Osteogenesis Imperfecta Type XIV

Mendelian MONDO:0014029 Pathograph 3 Show in embeddings browser Osteogenesis imperfecta

Osteogenesis imperfecta type XIV (OI type XIV) is a rare autosomal recessive brittle bone disease caused by biallelic null mutations in TMEM38B, the gene encoding TRIC-B, a trimeric intracellular cation channel of the endoplasmic-reticulum (ER) membrane that is specific for monovalent cations (potassium). TRIC-B is proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores by providing a counter-ionic K+ flux. Loss of TRIC-B disrupts the kinetics of ER calcium release and store-operated calcium entry, causing ER stress and dysregulating type I collagen synthesis at multiple steps — altered helical lysine and telopeptide hydroxylation, delayed procollagen chain assembly, intracellular retention of misfolded collagen, and markedly reduced collagen secretion — so that the bone extracellular matrix is insufficient even though the collagen that is incorporated is of near-normal stability. The disorder was first defined as a novel autosomal recessive OI locus on chromosome 9q31 by a TMEM38B mutation in consanguineous Arabian families (Shaheen et al., 2012) and independently in Israeli Bedouin families (Volodarsky et al., 2013). Clinically it produces moderately severe OI with recurrent fractures, reduced bone mineral density (osteopenia), growth deficiency, and long-bone bowing/deformity. Tric-b-knockout mice and CRISPR-engineered TMEM38B-null human osteoblasts recapitulate the impaired ER Ca2+ handling, defective collagen secretion, and poor mineralization.

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1
Inheritance
3
Pathophys.
10
Phenotypes
3
Pathograph
1
Genes
3
Medical Actions
8
References
🏷

Classifications

ISDS Skeletal Nosology
osteogenesis imperfecta and decreased bone density
👪

Inheritance

1
Autosomal Recessive HP:0000007
Autosomal recessive inheritance from biallelic (homozygous) loss-of-function TMEM38B variants segregating in consanguineous kindreds; heterozygous carriers are clinically unaffected.
Autosomal recessive inheritance
Show evidence (2 references)
PMID:23316006 SUPPORT Human Clinical
"Autosomal recessive osteogenesis imperfecta (OI) was diagnosed in three unrelated Israeli Bedouin consanguineous families."
Establishes the autosomal recessive inheritance of OI type XIV from a biallelic TMEM38B deletion in consanguineous kindreds.
PMID:23054245 SUPPORT Human Clinical
"In three multiplex families, autozygosity and linkage analysis revealed a novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating deletion of exon 4 of TMEM38B was identified within that interval."
Independent consanguineous families confirming the recessive TMEM38B locus for OI type XIV.
⚙

Pathophysiology

3
TMEM38B Loss Eliminates the ER Cation Channel TRIC-B and Disrupts ER Calcium Flux
TMEM38B encodes TRIC-B, a trimeric intracellular cation channel of the endoplasmic-reticulum membrane that conducts monovalent cations (K+) and is proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores. Biallelic null mutations render TRIC-B protein undetectable in patient fibroblasts and osteoblasts. The loss impairs release of ER luminal Ca2+ and store-operated calcium entry; steady-state ER Ca2+ is unchanged, indicating that TRIC-B governs the kinetics of ER calcium depletion and recovery rather than the resting store level. The disturbed Ca2+ flux triggers ER stress with increased BiP.
osteoblast CL:0000062 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves osteoblast (CL:0000062). CL:0000062 is a cell type from the Cell Ontology. fibroblast CL:0000057 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves fibroblast (CL:0000057). CL:0000057 is a cell type from the Cell Ontology.
endoplasmic reticulum calcium ion homeostasis GO:0032469 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal endoplasmic reticulum calcium ion homeostasis (GO:0032469). GO:0032469 is a biological process from the Gene Ontology. ⚠ ABNORMAL calcium ion transport (ER Ca2+ release / store-operated entry) GO:0006816 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased calcium ion transport (ER Ca2+ release / store-operated entry), annotated with calcium ion transport (GO:0006816). GO:0006816 is a biological process from the Gene Ontology. ↓ DECREASED
Downstream
Dysregulated Collagen Synthesis and Defective Secretion The disturbed ER Ca2+ flux and ER stress dysregulate type I collagen synthesis, modification, folding, and secretion in osteoblasts.
Show evidence (3 references)
PMID:27441836 SUPPORT In Vitro
"TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores."
Defines TRIC-B as the ER monovalent cation channel encoded by TMEM38B that counterbalances ER Ca2+ release, the protein lost in OI type XIV.
PMID:27441836 SUPPORT In Vitro
"TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated with deficient store-operated calcium entry, although SERCA and IP3R have normal stability."
Documents the proximal lesion: TRIC-B loss impairs ER Ca2+ release and store-operated entry.
PMID:27441836 SUPPORT In Vitro
"Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency, supporting a role for TRIC-B in the kinetics of ER calcium depletion and recovery."
Clarifies that TRIC-B controls the kinetics of ER Ca2+ flux rather than the resting store level.
Dysregulated Collagen Synthesis and Defective Secretion
The disturbed Ca2+ flux dysregulates type I collagen synthesis at multiple steps. Collagen helical lysine hydroxylation is reduced while telopeptide hydroxylation is increased, reflecting altered activity of Ca2+-dependent collagen-modifying enzymes and chaperones (increased LH1, decreased FKBP65). Procollagen chain assembly is delayed and the resulting misfolded collagen is substantially retained intracellularly, producing a 50-70% reduction in secreted collagen. Lower-stability forms that escape proteasomal degradation are not incorporated into matrix, so collagen production — rather than collagen quality — is the primary deficit.
osteoblast CL:0000062 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves osteoblast (CL:0000062). CL:0000062 is a cell type from the Cell Ontology. fibroblast CL:0000057 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves fibroblast (CL:0000057). CL:0000057 is a cell type from the Cell Ontology.
collagen biosynthetic process GO:0032964 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal collagen biosynthetic process (GO:0032964). GO:0032964 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Downstream
Insufficient Bone Matrix, Reduced Mineralization, and Skeletal Fragility Reduced collagen secretion and impaired osteoblast function yield an insufficient, poorly mineralized bone matrix and skeletal fragility.
Show evidence (3 references)
PMID:27441836 SUPPORT In Vitro
"The disturbed Ca2+ flux causes ER stress and increased BiP, and dysregulates synthesis of proband type I collagen at multiple steps."
Links the impaired ER Ca2+ kinetics to ER stress and multi-step dysregulation of type I collagen synthesis.
PMID:27441836 SUPPORT In Vitro
"The resulting misfolded collagen is substantially retained in TRIC-B null cells, consistent with a 50-70% reduction in secreted collagen."
Documents intracellular retention of misfolded collagen and the major reduction in collagen secretion in TRIC-B null cells.
PMID:34582479 SUPPORT In Vitro
"Few clones were validated as good models for the disease since they reproduce the altered ER calcium flux, collagen I structure and impaired secretion and osteoblastic markers expression detected in patients' cells."
CRISPR TMEM38B-null human osteoblasts reproduce the altered ER Ca2+ flux and impaired collagen I secretion seen in patient cells.
Insufficient Bone Matrix, Reduced Mineralization, and Skeletal Fragility
Reduced collagen deposition and impaired osteoblast proliferation and function produce an insufficient bone extracellular matrix with poor mineralization, yielding low bone mineral density (osteopenia) and skeletal fragility. Clinically this manifests as recurrent fractures, growth deficiency, and long-bone bowing/deformity. Tric-b-knockout mice serve as an OI model in which deranged ER Ca2+ handling reduces ECM synthesis in osteoblasts, leading to poor mineralization.
osteoblast CL:0000062 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves osteoblast (CL:0000062). CL:0000062 is a cell type from the Cell Ontology. fibroblast CL:0000057 Cell Ontology (CL) Relation: this pathophysiological event involves this cell type This pathophysiological event involves fibroblast (CL:0000057). CL:0000057 is a cell type from the Cell Ontology.
bone mineralization GO:0030282 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves decreased bone mineralization (GO:0030282). GO:0030282 is a biological process from the Gene Ontology. ↓ DECREASED ossification GO:0001503 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves abnormal ossification (GO:0001503). GO:0001503 is a biological process from the Gene Ontology. ⚠ ABNORMAL
Show evidence (3 references)
PMID:38123563 SUPPORT Model Organism
"Serious mutations in the TRIC-B (also referred to as TMEM38B) locus cause autosomal recessive osteogenesis imperfecta (OI), which is characterized by insufficient bone mineralization."
Establishes insufficient bone mineralization as the defining skeletal consequence of TMEM38B/TRIC-B loss.
PMID:38123563 SUPPORT Model Organism
"Tric-b deficiency deranges ER Ca2+ handling and thus reduces extracellular matrix (ECM) synthesis in osteoblasts, leading to poor mineralization."
Links deranged ER Ca2+ handling to reduced osteoblast ECM synthesis and poor mineralization in the Tric-b-knockout OI model.
PMID:34582479 SUPPORT In Vitro
"Impaired proliferation and mineralization in KO clones unveiled the relevance of TRIC-B in osteoblasts functionality."
Demonstrates impaired osteoblast proliferation and mineralization on TMEM38B loss, underlying the bone fragility of OI type XIV.
⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Osteogenesis Imperfecta Type XIV Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
●

Phenotypes

10
Eye 1
Blue Sclerae HP:0000592 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Blue sclerae (HP:0000592). HP:0000592 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41465594 SUPPORT Human Clinical
"This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities."
Systematic review documents blue sclerae as a variable (not constant) feature of OI type XIV, present in some but not all TMEM38B patients.
Head and Neck 1
Dental Abnormalities Abnormality of the dentition HP:0000164 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dental abnormalities, annotated with Abnormality of the dentition (HP:0000164). HP:0000164 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41465594 SUPPORT Human Clinical
"This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities."
Systematic review of 56 OI type XIV patients documents dental abnormalities as a variable (not constant) feature of TMEM38B-related OI, completing the scleral/dental hallmark audit for this entry alongside the blue sclerae finding.
Limbs 2
Bowing of the Long Bones HP:0006487 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Bowing of the long bones (HP:0006487). HP:0006487 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27441836 SUPPORT Human Clinical
"bowing and fragility of long bones leading to multiple fractures in infancy"
Documents bowing of the long bones as a clinical feature of TMEM38B/TRIC-B OI type XIV.
Coxa Vara HP:0002812 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Coxa vara (HP:0002812). HP:0002812 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28323974 SUPPORT Human Clinical
"Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities)."
Documents coxa vara as a skeletal deformity in TMEM38B-related OI type XIV.
Musculoskeletal 5
Recurrent Fractures HP:0002757 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Recurrent fractures (HP:0002757). HP:0002757 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:23316006 SUPPORT Human Clinical
"Fractures were evident in all cases in infancy."
Documents fractures beginning in infancy as a defining clinical feature of TMEM38B-related OI type XIV.
Reduced Bone Mineral Density HP:0004349 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Reduced bone mineral density (HP:0004349). HP:0004349 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:34582479 SUPPORT In Vitro
"Osteogenesis imperfecta (OI) type XIV is a rare recessive bone disorder characterized by variable degree of severity associated to osteopenia."
Documents osteopenia (reduced bone mineral density) as a characteristic feature of OI type XIV.
Vertebral Compression Fractures HP:0002953 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Vertebral fractures, annotated with Vertebral compression fracture (HP:0002953). HP:0002953 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28323974 SUPPORT Human Clinical
"Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities)."
Natural-history study of eight OI type XIV patients documents vertebral fractures among the previously under-reported skeletal features of TMEM38B-related OI.
Muscular Hypotonia HP:0001252 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Muscular hypotonia, annotated with Hypotonia (HP:0001252). HP:0001252 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:28323974 SUPPORT Human Clinical
"Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities)."
Documents muscular hypotonia as an extraskeletal feature of OI type XIV, distinguishing it from purely skeletal collagen-defect OI.
Scoliosis HP:0002650 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Scoliosis (HP:0002650). HP:0002650 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:41465594 SUPPORT Human Clinical
"This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities."
Systematic review encompassing 56 OI type XIV patients documents scoliosis among the core skeletal features of TMEM38B-related OI.
Growth 1
Growth Deficiency Growth delay HP:0001510 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Growth delay (HP:0001510). HP:0001510 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:20301472 SUPPORT Human Clinical
"short stature"
Short stature (growth deficiency) is a recognized feature of the osteogenesis imperfecta phenotype that applies to OI type XIV.
🧬

Genetic Associations

1
TMEM38B (TRIC-B) Loss-of-Function Mutations (Causative)
Gene: TMEM38B (TRIC-B, ER monovalent cation channel) hgnc:25535 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is TMEM38B (TRIC-B, ER monovalent cation channel), annotated with TMEM38B (hgnc:25535). hgnc:25535 is a gene from the HUGO Gene Nomenclature Committee.
Show evidence (3 references)
PMID:23054245 SUPPORT Human Clinical
"In three multiplex families, autozygosity and linkage analysis revealed a novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating deletion of exon 4 of TMEM38B was identified within that interval."
Identifies the causative truncating TMEM38B exon 4 deletion defining the novel recessive OI locus (OI type XIV).
PMID:23316006 SUPPORT Human Clinical
"a homozygous deletion mutation of exon 4 of TMEM38B, leading to an early stop codon and a truncated protein, as well as low TMEM38B mRNA levels."
Independent confirmation of a homozygous loss-of-function TMEM38B exon 4 deletion causing recessive OI.
PMID:23316006 SUPPORT Human Clinical
"TMEM38B encodes TRIC-B, a ubiquitous component of TRIC, a monovalent cation-specific channel involved in Ca(2+) release from intracellular stores"
Documents that TMEM38B encodes the monovalent cation channel TRIC-B involved in intracellular Ca2+ release.
💊

Medical Actions

3
Bisphosphonate Therapy
Action: Bisphosphonate TherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Bisphosphonate Therapy (NCIT:C198585). NCIT:C198585 is a clinical intervention from the NCI Thesaurus. NCIT:C198585
Intravenous bisphosphonates (e.g., pamidronate, zoledronic acid) are the pharmacological mainstay of severe OI, increasing bone mineral density and reducing fracture frequency. They are antiresorptive and do not correct the underlying ER calcium-channel defect.
Show evidence (2 references)
PMID:20301472 SUPPORT Human Clinical
"Bisphosphonates continue to be used most extensively in those with vertebral fractures, frequent long bone fractures, or more severe OI."
GeneReviews documents bisphosphonates as the mainstay pharmacotherapy for OI with frequent fractures or more severe disease, the management category that applies to OI type XIV.
PMID:28323974 SUPPORT Human Clinical
"Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities."
OI-type-XIV-specific evidence: the TMEM38B natural-history cohort documents probands as responsive to bisphosphonate therapy (lumbar spine bone density z score increased following treatment).
Orthopedic Surgery and Intramedullary Rodding
Action: surgical procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is surgical procedure (NCIT:C15329). NCIT:C15329 is a clinical intervention from the NCI Thesaurus. Ontology label: Surgical Procedure NCIT:C15329
Intramedullary (telescoping) rod fixation and corrective osteotomy stabilize fracture-prone, deformed long bones; spinal surgery addresses progressive scoliosis.
Show evidence (1 reference)
PMID:20301472 SUPPORT Human Clinical
"intramedullary rodding when indicated to provide anatomic positioning of limbs"
GeneReviews documents intramedullary rodding as standard orthopedic management for OI long-bone fractures and deformity.
Physical Therapy and Rehabilitation
Action: physical therapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is physical therapy (NCIT:C15302). NCIT:C15302 is a clinical intervention from the NCI Thesaurus. Ontology label: Physical Therapy NCIT:C15302
Physical and occupational therapy improve mobility and muscle strength and prevent contractures and deformity; early physical therapy follows brief post-fracture immobilization.
Show evidence (1 reference)
PMID:20301472 SUPPORT Human Clinical
"Fractures are treated with as short a period of immobility as is practical, small and lightweight casts, and physical therapy as soon as casts are removed"
GeneReviews documents early physical therapy and brief immobilization as part of standard OI fracture rehabilitation.
🔬

Diagnosis

1
Molecular Genetic Diagnosis
OI type XIV is suspected in an infant or child with recessive OI (recurrent fractures from infancy, osteopenia, deformity) when COL1A1/COL1A2 and other recessive OI genes are negative. Diagnosis is confirmed by identifying biallelic loss-of-function TMEM38B variants by gene-panel or exome sequencing; supportive cellular findings include undetectable TRIC-B protein with altered ER Ca2+ flux and reduced collagen secretion in patient cells.
molecular genetic testing NCIT:C19770 NCI Thesaurus (NCIT)
Show evidence (1 reference)
PMID:23054245 SUPPORT Human Clinical
"We used autozygome guided mutation analysis of AR OI (AR OI) genes followed by exome sequencing when such analysis failed to identify the causative mutation."
Molecular genetic testing (autozygosity mapping and exome sequencing) establishes the TMEM38B diagnosis of OI type XIV.
{ }

Source YAML

click to show 
name: Osteogenesis Imperfecta Type XIV
creation_date: "2026-06-30T00:00:00Z"
category: Mendelian
disease_term:
  preferred_term: Osteogenesis imperfecta type 14
  term:
    id: MONDO:0014029
    label: osteogenesis imperfecta type 14
description: >-
  Osteogenesis imperfecta type XIV (OI type XIV) is a rare autosomal recessive
  brittle bone disease caused by biallelic null mutations in TMEM38B, the gene
  encoding TRIC-B, a trimeric intracellular cation channel of the
  endoplasmic-reticulum (ER) membrane that is specific for monovalent cations
  (potassium). TRIC-B is proposed to counterbalance IP3R-mediated Ca2+ release
  from intracellular stores by providing a counter-ionic K+ flux. Loss of TRIC-B
  disrupts the kinetics of ER calcium release and store-operated calcium entry,
  causing ER stress and dysregulating type I collagen synthesis at multiple
  steps — altered helical lysine and telopeptide hydroxylation, delayed
  procollagen chain assembly, intracellular retention of misfolded collagen, and
  markedly reduced collagen secretion — so that the bone extracellular matrix is
  insufficient even though the collagen that is incorporated is of near-normal
  stability. The disorder was first defined as a novel autosomal recessive OI
  locus on chromosome 9q31 by a TMEM38B mutation in consanguineous Arabian
  families (Shaheen et al., 2012) and independently in Israeli Bedouin families
  (Volodarsky et al., 2013). Clinically it produces moderately severe OI with
  recurrent fractures, reduced bone mineral density (osteopenia), growth
  deficiency, and long-bone bowing/deformity. Tric-b-knockout mice and
  CRISPR-engineered TMEM38B-null human osteoblasts recapitulate the impaired ER
  Ca2+ handling, defective collagen secretion, and poor mineralization.
parents:
- Osteogenesis imperfecta
inheritance:
- name: Autosomal Recessive
  description: >-
    Autosomal recessive inheritance from biallelic (homozygous) loss-of-function
    TMEM38B variants segregating in consanguineous kindreds; heterozygous
    carriers are clinically unaffected.
  inheritance_term:
    preferred_term: Autosomal recessive inheritance
    term:
      id: HP:0000007
      label: Autosomal recessive inheritance
  evidence:
  - reference: PMID:23316006
    reference_title: "A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Autosomal recessive osteogenesis imperfecta (OI) was diagnosed in three
      unrelated Israeli Bedouin consanguineous families.
    explanation: >-
      Establishes the autosomal recessive inheritance of OI type XIV from a
      biallelic TMEM38B deletion in consanguineous kindreds.
  - reference: PMID:23054245
    reference_title: "Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In three multiplex families, autozygosity and linkage analysis revealed a
      novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating
      deletion of exon 4 of TMEM38B was identified within that interval.
    explanation: >-
      Independent consanguineous families confirming the recessive TMEM38B locus
      for OI type XIV.
classifications:
  isds_skeletal_category:
  - classification_value: osteogenesis_imperfecta_and_decreased_bone_density
    notes: >-
      ISDS Nosology and Classification of Genetic Skeletal Disorders, 2019
      revision (Mortier et al., PMID:31633310), Table 1 group 25 "Osteogenesis
      Imperfecta and decreased bone density group"; this entry corresponds to the
      phenotypic osteogenesis imperfecta entries (OI types 1-5), which the
      nosology lists by clinical severity rather than by the gene-numbered OI type
      used for this entry.
pathophysiology:
- name: TMEM38B Loss Eliminates the ER Cation Channel TRIC-B and Disrupts ER Calcium Flux
  description: >-
    TMEM38B encodes TRIC-B, a trimeric intracellular cation channel of the
    endoplasmic-reticulum membrane that conducts monovalent cations (K+) and is
    proposed to counterbalance IP3R-mediated Ca2+ release from intracellular
    stores. Biallelic null mutations render TRIC-B protein undetectable in
    patient fibroblasts and osteoblasts. The loss impairs release of ER luminal
    Ca2+ and store-operated calcium entry; steady-state ER Ca2+ is unchanged,
    indicating that TRIC-B governs the kinetics of ER calcium depletion and
    recovery rather than the resting store level. The disturbed Ca2+ flux
    triggers ER stress with increased BiP.
  cell_types:
  - preferred_term: osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: endoplasmic reticulum calcium ion homeostasis
    term:
      id: GO:0032469
      label: endoplasmic reticulum calcium ion homeostasis
    modifier: ABNORMAL
  - preferred_term: calcium ion transport (ER Ca2+ release / store-operated entry)
    term:
      id: GO:0006816
      label: calcium ion transport
    modifier: DECREASED
  evidence:
  - reference: PMID:27441836
    reference_title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B,
      proposed to counterbalance IP3R-mediated Ca2+ release from intracellular
      stores.
    explanation: >-
      Defines TRIC-B as the ER monovalent cation channel encoded by TMEM38B that
      counterbalances ER Ca2+ release, the protein lost in OI type XIV.
  - reference: PMID:27441836
    reference_title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      TRIC-B deficiency causes impaired release of ER luminal Ca2+, associated
      with deficient store-operated calcium entry, although SERCA and IP3R have
      normal stability.
    explanation: >-
      Documents the proximal lesion: TRIC-B loss impairs ER Ca2+ release and
      store-operated entry.
  - reference: PMID:27441836
    reference_title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Notably, steady state ER Ca2+ is unchanged in TRIC-B deficiency,
      supporting a role for TRIC-B in the kinetics of ER calcium depletion and
      recovery.
    explanation: >-
      Clarifies that TRIC-B controls the kinetics of ER Ca2+ flux rather than
      the resting store level.
  downstream:
  - target: Dysregulated Collagen Synthesis and Defective Secretion
    description: >-
      The disturbed ER Ca2+ flux and ER stress dysregulate type I collagen
      synthesis, modification, folding, and secretion in osteoblasts.
- name: Dysregulated Collagen Synthesis and Defective Secretion
  description: >-
    The disturbed Ca2+ flux dysregulates type I collagen synthesis at multiple
    steps. Collagen helical lysine hydroxylation is reduced while telopeptide
    hydroxylation is increased, reflecting altered activity of Ca2+-dependent
    collagen-modifying enzymes and chaperones (increased LH1, decreased FKBP65).
    Procollagen chain assembly is delayed and the resulting misfolded collagen is
    substantially retained intracellularly, producing a 50-70% reduction in
    secreted collagen. Lower-stability forms that escape proteasomal degradation
    are not incorporated into matrix, so collagen production — rather than
    collagen quality — is the primary deficit.
  cell_types:
  - preferred_term: osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: collagen biosynthetic process
    term:
      id: GO:0032964
      label: collagen biosynthetic process
    modifier: ABNORMAL
  evidence:
  - reference: PMID:27441836
    reference_title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The disturbed Ca2+ flux causes ER stress and increased BiP, and
      dysregulates synthesis of proband type I collagen at multiple steps.
    explanation: >-
      Links the impaired ER Ca2+ kinetics to ER stress and multi-step
      dysregulation of type I collagen synthesis.
  - reference: PMID:27441836
    reference_title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      The resulting misfolded collagen is substantially retained in TRIC-B null
      cells, consistent with a 50-70% reduction in secreted collagen.
    explanation: >-
      Documents intracellular retention of misfolded collagen and the major
      reduction in collagen secretion in TRIC-B null cells.
  - reference: PMID:34582479
    reference_title: "Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Few clones were validated as good models for the disease since they
      reproduce the altered ER calcium flux, collagen I structure and impaired
      secretion and osteoblastic markers expression detected in patients' cells.
    explanation: >-
      CRISPR TMEM38B-null human osteoblasts reproduce the altered ER Ca2+ flux
      and impaired collagen I secretion seen in patient cells.
  downstream:
  - target: Insufficient Bone Matrix, Reduced Mineralization, and Skeletal Fragility
    description: >-
      Reduced collagen secretion and impaired osteoblast function yield an
      insufficient, poorly mineralized bone matrix and skeletal fragility.
- name: Insufficient Bone Matrix, Reduced Mineralization, and Skeletal Fragility
  description: >-
    Reduced collagen deposition and impaired osteoblast proliferation and
    function produce an insufficient bone extracellular matrix with poor
    mineralization, yielding low bone mineral density (osteopenia) and skeletal
    fragility. Clinically this manifests as recurrent fractures, growth
    deficiency, and long-bone bowing/deformity. Tric-b-knockout mice serve as an
    OI model in which deranged ER Ca2+ handling reduces ECM synthesis in
    osteoblasts, leading to poor mineralization.
  cell_types:
  - preferred_term: osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  - preferred_term: fibroblast
    term:
      id: CL:0000057
      label: fibroblast
  biological_processes:
  - preferred_term: bone mineralization
    term:
      id: GO:0030282
      label: bone mineralization
    modifier: DECREASED
  - preferred_term: ossification
    term:
      id: GO:0001503
      label: ossification
    modifier: ABNORMAL
  evidence:
  - reference: PMID:38123563
    reference_title: "Atypical cell death and insufficient matrix organization in long-bone growth plates from Tric-b-knockout mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Serious mutations in the TRIC-B (also referred to as TMEM38B) locus cause
      autosomal recessive osteogenesis imperfecta (OI), which is characterized by
      insufficient bone mineralization.
    explanation: >-
      Establishes insufficient bone mineralization as the defining skeletal
      consequence of TMEM38B/TRIC-B loss.
  - reference: PMID:38123563
    reference_title: "Atypical cell death and insufficient matrix organization in long-bone growth plates from Tric-b-knockout mice."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: >-
      Tric-b deficiency deranges ER Ca2+ handling and thus reduces extracellular
      matrix (ECM) synthesis in osteoblasts, leading to poor mineralization.
    explanation: >-
      Links deranged ER Ca2+ handling to reduced osteoblast ECM synthesis and
      poor mineralization in the Tric-b-knockout OI model.
  - reference: PMID:34582479
    reference_title: "Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Impaired proliferation and mineralization in KO clones unveiled the
      relevance of TRIC-B in osteoblasts functionality.
    explanation: >-
      Demonstrates impaired osteoblast proliferation and mineralization on
      TMEM38B loss, underlying the bone fragility of OI type XIV.
genetic:
- name: TMEM38B (TRIC-B) Loss-of-Function Mutations
  association: Causative
  gene_term:
    preferred_term: TMEM38B (TRIC-B, ER monovalent cation channel)
    term:
      id: hgnc:25535
      label: TMEM38B
  notes: >-
    OI type XIV is caused by biallelic null (loss-of-function) variants in
    TMEM38B on chromosome 9q31, the gene encoding the ER cation channel TRIC-B.
    The originally reported alleles are a homozygous truncating deletion of exon
    4 in consanguineous Arabian families (Shaheen et al., 2012) and an
    independent homozygous exon 4 deletion producing an early stop codon and low
    TMEM38B mRNA in Israeli Bedouin families (Volodarsky et al., 2013). TRIC-B
    protein is undetectable in patient fibroblasts and osteoblasts.
  evidence:
  - reference: PMID:23054245
    reference_title: "Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In three multiplex families, autozygosity and linkage analysis revealed a
      novel recessive OI locus on chromosome 9q31.1-31.3, and a novel truncating
      deletion of exon 4 of TMEM38B was identified within that interval.
    explanation: >-
      Identifies the causative truncating TMEM38B exon 4 deletion defining the
      novel recessive OI locus (OI type XIV).
  - reference: PMID:23316006
    reference_title: "A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      a homozygous deletion mutation of exon 4 of TMEM38B, leading to an early
      stop codon and a truncated protein, as well as low TMEM38B mRNA levels.
    explanation: >-
      Independent confirmation of a homozygous loss-of-function TMEM38B exon 4
      deletion causing recessive OI.
  - reference: PMID:23316006
    reference_title: "A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      TMEM38B encodes TRIC-B, a ubiquitous component of TRIC, a monovalent
      cation-specific channel involved in Ca(2+) release from intracellular
      stores
    explanation: >-
      Documents that TMEM38B encodes the monovalent cation channel TRIC-B
      involved in intracellular Ca2+ release.
phenotypes:
- name: Recurrent Fractures
  description: >-
    Bone fragility with recurrent fractures, evident in infancy, the cardinal
    feature of OI type XIV.
  phenotype_term:
    preferred_term: Recurrent fractures
    term:
      id: HP:0002757
      label: Recurrent fractures
  evidence:
  - reference: PMID:23316006
    reference_title: "A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Fractures were evident in all cases in infancy.
    explanation: >-
      Documents fractures beginning in infancy as a defining clinical feature of
      TMEM38B-related OI type XIV.
- name: Reduced Bone Mineral Density
  description: >-
    Low bone mineral density (osteopenia) reflecting the insufficient, poorly
    mineralized bone matrix produced by TRIC-B deficiency.
  phenotype_term:
    preferred_term: Reduced bone mineral density
    term:
      id: HP:0004349
      label: Reduced bone mineral density
  evidence:
  - reference: PMID:34582479
    reference_title: "Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV."
    supports: SUPPORT
    evidence_source: IN_VITRO
    snippet: >-
      Osteogenesis imperfecta (OI) type XIV is a rare recessive bone disorder
      characterized by variable degree of severity associated to osteopenia.
    explanation: >-
      Documents osteopenia (reduced bone mineral density) as a characteristic
      feature of OI type XIV.
- name: Growth Deficiency
  description: >-
    Growth deficiency with short stature, part of the moderately severe OI
    phenotype caused by TMEM38B deficiency.
  phenotype_term:
    preferred_term: Growth delay
    term:
      id: HP:0001510
      label: Growth delay
  evidence:
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      short stature
    explanation: >-
      Short stature (growth deficiency) is a recognized feature of the
      osteogenesis imperfecta phenotype that applies to OI type XIV.
- name: Bowing of the Long Bones
  description: >-
    Bowing and deformity of the long bones accompany the fragility and recurrent
    fractures, reflecting the mechanically weak, undermineralized bone.
  phenotype_term:
    preferred_term: Bowing of the long bones
    term:
      id: HP:0006487
      label: Bowing of the long bones
  evidence:
  - reference: PMID:27441836
    reference_title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      bowing and fragility of long bones leading to multiple fractures in
      infancy
    explanation: >-
      Documents bowing of the long bones as a clinical feature of TMEM38B/TRIC-B
      OI type XIV.
- name: Vertebral Compression Fractures
  description: >-
    Vertebral fractures occur in OI type XIV, contributing to reduced spinal bone
    density. Recognized as a previously under-reported skeletal feature in the
    natural-history study of TMEM38B patients.
  phenotype_term:
    preferred_term: Vertebral fractures
    term:
      id: HP:0002953
      label: Vertebral compression fracture
  evidence:
  - reference: PMID:28323974
    reference_title: "Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Previously unreported features include vertebral fractures, periosteal
      cloaking, coxa vara, and extraskeletal features (muscular hypotonia,
      cardiac abnormalities).
    explanation: >-
      Natural-history study of eight OI type XIV patients documents vertebral
      fractures among the previously under-reported skeletal features of
      TMEM38B-related OI.
- name: Coxa Vara
  description: >-
    Coxa vara (reduced femoral neck-shaft angle) is a skeletal deformity
    documented in OI type XIV, part of the previously under-reported feature set
    from the TMEM38B natural-history cohort.
  phenotype_term:
    preferred_term: Coxa vara
    term:
      id: HP:0002812
      label: Coxa vara
  evidence:
  - reference: PMID:28323974
    reference_title: "Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Previously unreported features include vertebral fractures, periosteal
      cloaking, coxa vara, and extraskeletal features (muscular hypotonia,
      cardiac abnormalities).
    explanation: >-
      Documents coxa vara as a skeletal deformity in TMEM38B-related OI type XIV.
- name: Muscular Hypotonia
  description: >-
    Muscular hypotonia is an extraskeletal feature reported in OI type XIV,
    plausibly related to the intracellular calcium-flux abnormality caused by
    TRIC-B loss (TRIC channels also participate in muscle Ca2+ handling).
  phenotype_term:
    preferred_term: Muscular hypotonia
    term:
      id: HP:0001252
      label: Hypotonia
  evidence:
  - reference: PMID:28323974
    reference_title: "Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Previously unreported features include vertebral fractures, periosteal
      cloaking, coxa vara, and extraskeletal features (muscular hypotonia,
      cardiac abnormalities).
    explanation: >-
      Documents muscular hypotonia as an extraskeletal feature of OI type XIV,
      distinguishing it from purely skeletal collagen-defect OI.
- name: Scoliosis
  description: >-
    Scoliosis is a recurrent spinal deformity in OI type XIV, part of the
    skeletal-deformity spectrum reported across the aggregated TMEM38B patient
    cohort.
  phenotype_term:
    preferred_term: Scoliosis
    term:
      id: HP:0002650
      label: Scoliosis
  evidence:
  - reference: PMID:41465594
    reference_title: "Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This leads to severe bone fragility, early-onset fractures, skeletal
      deformities, low bone mass, scoliosis, and variable features like blue
      sclerae or dental abnormalities.
    explanation: >-
      Systematic review encompassing 56 OI type XIV patients documents scoliosis
      among the core skeletal features of TMEM38B-related OI.
- name: Blue Sclerae
  description: >-
    Blue sclerae are a variable, inconsistently reported feature of OI type XIV.
    Unlike classic dominant collagen-defect OI, many TMEM38B patients have normal
    (white) sclerae, so blue sclerae are captured here as a variable finding
    rather than a constant feature.
  phenotype_term:
    preferred_term: Blue sclerae
    term:
      id: HP:0000592
      label: Blue sclerae
  evidence:
  - reference: PMID:41465594
    reference_title: "Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This leads to severe bone fragility, early-onset fractures, skeletal
      deformities, low bone mass, scoliosis, and variable features like blue
      sclerae or dental abnormalities.
    explanation: >-
      Systematic review documents blue sclerae as a variable (not constant)
      feature of OI type XIV, present in some but not all TMEM38B patients.
- name: Dental Abnormalities
  description: >-
    Dental abnormalities are a variable, inconsistently reported feature of OI
    type XIV. As with blue sclerae, they are not a constant finding across the
    aggregated TMEM38B cohort — many patients have normal dentition — so dental
    involvement is captured here as a variable finding. The generic dentition
    term is used because the systematic review reports "dental abnormalities"
    without specifying dentinogenesis imperfecta.
  phenotype_term:
    preferred_term: Dental abnormalities
    term:
      id: HP:0000164
      label: Abnormality of the dentition
  evidence:
  - reference: PMID:41465594
    reference_title: "Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      This leads to severe bone fragility, early-onset fractures, skeletal
      deformities, low bone mass, scoliosis, and variable features like blue
      sclerae or dental abnormalities.
    explanation: >-
      Systematic review of 56 OI type XIV patients documents dental
      abnormalities as a variable (not constant) feature of TMEM38B-related OI,
      completing the scleral/dental hallmark audit for this entry alongside the
      blue sclerae finding.
diagnosis:
- name: Molecular Genetic Diagnosis
  description: >-
    OI type XIV is suspected in an infant or child with recessive OI (recurrent
    fractures from infancy, osteopenia, deformity) when COL1A1/COL1A2 and other
    recessive OI genes are negative. Diagnosis is confirmed by identifying
    biallelic loss-of-function TMEM38B variants by gene-panel or exome
    sequencing; supportive cellular findings include undetectable TRIC-B protein
    with altered ER Ca2+ flux and reduced collagen secretion in patient cells.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: NCIT:C19770
      label: Molecular Analysis
  evidence:
  - reference: PMID:23054245
    reference_title: "Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      We used autozygome guided mutation analysis of AR OI (AR OI) genes
      followed by exome sequencing when such analysis failed to identify the
      causative mutation.
    explanation: >-
      Molecular genetic testing (autozygosity mapping and exome sequencing)
      establishes the TMEM38B diagnosis of OI type XIV.
treatments:
- name: Bisphosphonate Therapy
  description: >-
    Intravenous bisphosphonates (e.g., pamidronate, zoledronic acid) are the
    pharmacological mainstay of severe OI, increasing bone mineral density and
    reducing fracture frequency. They are antiresorptive and do not correct the
    underlying ER calcium-channel defect.
  treatment_term:
    preferred_term: Bisphosphonate Therapy
    term:
      id: NCIT:C198585
      label: Bisphosphonate Therapy
  evidence:
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Bisphosphonates continue to be used most extensively in those with
      vertebral fractures, frequent long bone fractures, or more severe OI.
    explanation: >-
      GeneReviews documents bisphosphonates as the mainstay pharmacotherapy for
      OI with frequent fractures or more severe disease, the management category
      that applies to OI type XIV.
  - reference: PMID:28323974
    reference_title: "Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Probands are responsive to bisphosphonates and some show muscular and
      cardiovascular features possibly related to intracellular calcium flux
      abnormalities.
    explanation: >-
      OI-type-XIV-specific evidence: the TMEM38B natural-history cohort documents
      probands as responsive to bisphosphonate therapy (lumbar spine bone density
      z score increased following treatment).
- name: Orthopedic Surgery and Intramedullary Rodding
  description: >-
    Intramedullary (telescoping) rod fixation and corrective osteotomy stabilize
    fracture-prone, deformed long bones; spinal surgery addresses progressive
    scoliosis.
  therapeutic_modality: SURGERY
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  evidence:
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      intramedullary rodding when
      indicated to provide anatomic positioning of limbs
    explanation: >-
      GeneReviews documents intramedullary rodding as standard orthopedic
      management for OI long-bone fractures and deformity.
- name: Physical Therapy and Rehabilitation
  description: >-
    Physical and occupational therapy improve mobility and muscle strength and
    prevent contractures and deformity; early physical therapy follows brief
    post-fracture immobilization.
  therapeutic_modality: BEHAVIORAL
  treatment_term:
    preferred_term: physical therapy
    term:
      id: NCIT:C15302
      label: Physical Therapy
  evidence:
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Fractures are treated with as
      short a period of immobility as is practical, small and lightweight casts, and
      physical therapy as soon as casts are removed
    explanation: >-
      GeneReviews documents early physical therapy and brief immobilization as
      part of standard OI fracture rehabilitation.
datasets: []
references:
- reference: PMID:23054245
  title: "Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation."
- reference: PMID:23316006
  title: "A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta."
- reference: PMID:27441836
  title: "Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta."
- reference: PMID:34582479
  title: "Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV."
- reference: PMID:38123563
  title: "Atypical cell death and insufficient matrix organization in long-bone growth plates from Tric-b-knockout mice."
- reference: PMID:20301472
  title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
  tags:
  - GeneReviews
- reference: PMID:28323974
  title: "Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect."
- reference: PMID:41465594
  title: "Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature."
📚

References & Deep Research

References

8
PMID:23054245
Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation.
No top-level findings curated for this source.
PMID:23316006
A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta.
No top-level findings curated for this source.
PMID:27441836
Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.
No top-level findings curated for this source.
PMID:34582479
Knocking out TMEM38B in human foetal osteoblasts hFOB 1.19 by CRISPR/Cas9: A model for recessive OI type XIV.
No top-level findings curated for this source.
PMID:38123563
Atypical cell death and insufficient matrix organization in long-bone growth plates from Tric-b-knockout mice.
No top-level findings curated for this source.
PMID:20301472
COL1A1- and COL1A2-Related Osteogenesis Imperfecta.
No top-level findings curated for this source.
PMID:28323974
Phenotypic Spectrum in Osteogenesis Imperfecta Due to Mutations in TMEM38B: Unraveling a Complex Cellular Defect.
No top-level findings curated for this source.
PMID:41465594
Previously Unreported TMEM38B Variant in Osteogenesis Imperfecta Type XIV: A Case Report and Systematic Review of the Literature.
No top-level findings curated for this source.