Osteogenesis Imperfecta Type I

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Inheritance

1

Autosomal Dominant

Autosomal dominant inheritance with high penetrance but variable expressivity. Most cases are inherited from an affected parent; de novo mutations also occur.

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Pathophysiology

1

Type I Collagen Haploinsufficiency

Null mutations in COL1A1 (nonsense, frameshift, splice site mutations causing nonsense-mediated mRNA decay) result in ~50% reduction in type I collagen production. The collagen that is produced has normal structure, explaining the milder phenotype compared to dominant-negative structural mutations.

Osteoblast link

Collagen Fibril Organization link Bone Development link

Show evidence (2 references)

PMID:1353940 SUPPORT Human Clinical

"Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type I produce about half the normal amount of type I procollagen, as a result of decreased synthesis of one of its constituent chains, pro alpha 1 (I)."

Landmark paper demonstrating that OI type I results from 50% reduced type I procollagen synthesis due to diminished pro alpha 1(I) chain production.

PMID:23529829 SUPPORT Human Clinical

"COL1A1 haploinsufficiency mutations lead to the mildest form of osteogenesis imperfecta (OI), OI type I."

Large clinical study (86 patients) confirming that COL1A1 haploinsufficiency specifically causes the mild type I phenotype.

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Phenotypes

6

Ear 1

Hearing Impairment Hearing impairment (HP:0000365)

Show evidence (1 reference)

PMID:11276328 SUPPORT Human Clinical

"It was found that the most common age of onset was in the second, third and fourth decades of life. At the age of 50 approximately 50 per cent of the patients had symptoms of hearing impairment; over the next 20 years there was little further increase. Differences were shown between patients..."

Large OI survey showing typical adult onset of hearing impairment and demonstrating that hearing loss is more common in type I than in type IV disease.

Eye 1

Blue Sclerae Blue sclerae (HP:0000592)

Show evidence (1 reference)

PMID:6954526 SUPPORT Human Clinical

"Type I osteogenesis imperfecta (OI) is a dominantly inherited disease characterized clinically by bone fractures during childhood, blue sclerae, and frequent hearing loss accompanied by a decreased content of type I collagen in bone and skin."

Landmark type I OI study identifying blue sclerae as part of the classic clinical phenotype.

Head and Neck 1

Dentinogenesis Imperfecta Dentinogenesis imperfecta (HP:0000703)

Show evidence (1 reference)

PMID:20384825 SUPPORT Human Clinical

"RESULTS: A total of ten patients had abnormal discolourations referable to DI: four patients were affected by OI type I, three patients by OI type III, and three patients by OI type IV."

Pediatric cohort directly documenting dentinogenesis imperfecta in children with type I OI.

Musculoskeletal 3

Recurrent Fractures Recurrent fractures (HP:0002757)

Show evidence (1 reference)

PMID:23529829 SUPPORT Human Clinical

"The average rate of long-bone fracture (femur, tibia/fibula, humerus, radius/ulna) in pediatric patients was 0.62 fractures per year, one-half of which affected the tibia/fibula. Long-bone fracture rate was negatively associated with age and lumbar spine areal bone mineral density."

Quantifies fracture rate in COL1A1 haploinsufficiency patients and confirms that fracture frequency decreases with age.

Vertebral Compression Fractures FREQUENT Vertebral compression fracture (HP:0002953)

Show evidence (1 reference)

PMID:23529829 SUPPORT Human Clinical

"Vertebral compression fractures were observed in 71% of the 58 pediatric patients who had lateral spine radiographs."

This cohort shows that vertebral compression fractures are a frequent and clinically important component of the type I OI skeletal phenotype.

Scoliosis OCCASIONAL Scoliosis (HP:0002650)

Show evidence (1 reference)

PMID:23529829 SUPPORT Human Clinical

"Scoliosis was present in about 30% of pediatric patients but the Cobb angle was <30 degrees in all cases."

Supports scoliosis as an occasional and usually mild spinal manifestation in pediatric type I OI.

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Genetic Associations

1

COL1A1 Null Mutations (Causative)

Show evidence (2 references)

PMID:1353940 SUPPORT Human Clinical

"In each case there was marked diminution in steady-state mRNA levels from one COL1A1 allele. Loss of an allele through deletion or rearrangement was not the cause of the diminished COL1A1 mRNA levels."

Study of 23 individuals from 21 families showed null allele-associated mRNA reduction, establishing the molecular basis of COL1A1 haploinsufficiency.

PMID:9443882 SUPPORT Human Clinical

"Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I."

Demonstrates that OI type I is specifically associated with COL1A1 mutations, with common null-allele mutation sequences identified.

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Treatments

3

Bisphosphonate Therapy

Action: Bisphosphonate therapy Ontology label: bisphosphonate agent therapy MAXO:0000954

Bisphosphonate therapy is used clinically in the management of skeletal fragility in osteogenesis imperfecta, particularly in children.

Physical Therapy

Action: Physical therapy Ontology label: physical therapy MAXO:0000011

Exercise and physical therapy to strengthen muscles and improve mobility while protecting fragile bones.

Fracture Management

Action: Orthopedic surgery Ontology label: surgical procedure MAXO:0000004

Standard orthopedic management of fractures with appropriate immobilization.

{ }

Source YAML

click to show

name: Osteogenesis Imperfecta Type I
creation_date: '2026-02-06T03:25:37Z'
updated_date: '2026-04-19T15:05:51Z'
category: Mendelian
description: >
  Osteogenesis imperfecta type I (OI type I) is the mildest form of osteogenesis
  imperfecta, caused by heterozygous null mutations in COL1A1 leading to quantitative
  deficiency of type I collagen (haploinsufficiency). Affected individuals have
  blue sclerae, mild bone fragility with variable fracture frequency, near-normal
  stature, and may develop hearing loss in adulthood. Unlike the more severe OI
  types caused by structural collagen mutations, type I results from reduced
  collagen quantity rather than abnormal collagen structure.
disease_term:
  preferred_term: Osteogenesis imperfecta type I
  term:
    id: MONDO:0008146
    label: osteogenesis imperfecta type 1
parents:
- Osteogenesis imperfecta
inheritance:
- name: Autosomal Dominant
  description: >
    Autosomal dominant inheritance with high penetrance but variable expressivity.
    Most cases are inherited from an affected parent; de novo mutations also occur.
prevalence:
- population: Swedish population-based registry
  percentage: 5.16 per 100,000
  notes: >-
    Population-based Swedish data identified type I as the most prevalent major
    osteogenesis imperfecta subtype, exceeding types III and IV.
  evidence:
  - reference: PMID:25944380
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The prevalence of OI types I, III, and IV was 5.16, 0.89, and 1.35/100 000, respectively (7.40/100 000 overall)"
    explanation: This population-based study provides a direct subtype-specific prevalence estimate for OI type I.
pathophysiology:
- name: Type I Collagen Haploinsufficiency
  description: >
    Null mutations in COL1A1 (nonsense, frameshift, splice site mutations causing
    nonsense-mediated mRNA decay) result in ~50% reduction in type I collagen
    production. The collagen that is produced has normal structure, explaining
    the milder phenotype compared to dominant-negative structural mutations.
  cell_types:
  - preferred_term: Osteoblast
    term:
      id: CL:0000062
      label: osteoblast
  biological_processes:
  - preferred_term: Collagen Fibril Organization
    term:
      id: GO:0030199
      label: collagen fibril organization
  - preferred_term: Bone Development
    term:
      id: GO:0060348
      label: bone development
  evidence:
  - reference: PMID:1353940
    reference_title: "Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Dermal fibroblasts from most individuals with osteogenesis imperfecta (OI) type
      I produce about half the normal amount of type I procollagen, as a result of
      decreased synthesis of one of its constituent chains, pro alpha 1 (I).
    explanation: >-
      Landmark paper demonstrating that OI type I results from 50% reduced type I
      procollagen synthesis due to diminished pro alpha 1(I) chain production.
  - reference: PMID:23529829
    reference_title: "Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      COL1A1 haploinsufficiency mutations lead to the mildest form of osteogenesis
      imperfecta (OI), OI type I.
    explanation: >-
      Large clinical study (86 patients) confirming that COL1A1 haploinsufficiency
      specifically causes the mild type I phenotype.
genetic:
- name: COL1A1 Null Mutations
  association: Causative
  notes: >
    Heterozygous null mutations in COL1A1 account for most OI type I cases.
    These include nonsense mutations, frameshift mutations, and splice site
    mutations that lead to nonsense-mediated decay of the mutant transcript.
    The 50% reduction in collagen quantity produces a milder phenotype than
    structural mutations.
  evidence:
  - reference: PMID:1353940
    reference_title: "Osteogenesis imperfecta type I is commonly due to a COL1A1 null allele of type I collagen."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      In each case there was marked diminution in steady-state mRNA levels from one
      COL1A1 allele. Loss of an allele through deletion or rearrangement was not the
      cause of the diminished COL1A1 mRNA levels.
    explanation: >-
      Study of 23 individuals from 21 families showed null allele-associated mRNA
      reduction, establishing the molecular basis of COL1A1 haploinsufficiency.
  - reference: PMID:9443882
    reference_title: "Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: identification of common sequences of null-allele mutations."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by
      conformation-sensitive gel electrophoresis identifies only COL1A1 mutations
      in
      15 patients with osteogenesis imperfecta type I.
    explanation: >-
      Demonstrates that OI type I is specifically associated with COL1A1 mutations,
      with common null-allele mutation sequences identified.
phenotypes:
- name: Blue Sclerae
  description: >
    Blue sclerae are a classic extraskeletal sign of osteogenesis imperfecta
    type I.
  phenotype_term:
    preferred_term: Blue sclerae
    term:
      id: HP:0000592
      label: Blue sclerae
  evidence:
  - reference: PMID:6954526
    reference_title: "Type I osteogenesis imperfecta: a nonfunctional allele for pro alpha 1 (I) chains of type I procollagen."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Type I osteogenesis imperfecta (OI) is a dominantly inherited disease
      characterized clinically by bone fractures during childhood, blue
      sclerae, and frequent hearing loss accompanied by a decreased content of
      type I collagen in bone and skin.
    explanation: >-
      Landmark type I OI study identifying blue sclerae as part of the classic
      clinical phenotype.
- name: Recurrent Fractures
  description: >
    Recurrent long-bone fractures are a core skeletal manifestation, and
    fracture rate declines with age.
  phenotype_term:
    preferred_term: Recurrent fractures
    term:
      id: HP:0002757
      label: Recurrent fractures
  evidence:
  - reference: PMID:23529829
    reference_title: "Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      The average rate of long-bone fracture (femur, tibia/fibula, humerus, radius/ulna)
      in pediatric patients was 0.62 fractures per year, one-half of which affected
      the tibia/fibula. Long-bone fracture rate was negatively associated with
      age and lumbar spine areal bone mineral density.
    explanation: >-
      Quantifies fracture rate in COL1A1 haploinsufficiency patients and confirms
      that fracture frequency decreases with age.
- name: Vertebral Compression Fractures
  description: >
    Vertebral compression fractures are frequent in growing patients with
    COL1A1 haploinsufficiency.
  phenotype_term:
    preferred_term: Vertebral compression fracture
    term:
      id: HP:0002953
      label: Vertebral compression fracture
  frequency: FREQUENT
  evidence:
  - reference: PMID:23529829
    reference_title: "Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Vertebral compression fractures were observed in 71% of the 58 pediatric
      patients who had lateral spine radiographs.
    explanation: >-
      This cohort shows that vertebral compression fractures are a frequent and
      clinically important component of the type I OI skeletal phenotype.
- name: Scoliosis
  description: >
    Mild scoliosis occurs in a substantial minority of pediatric patients.
  phenotype_term:
    preferred_term: Scoliosis
    term:
      id: HP:0002650
      label: Scoliosis
  frequency: OCCASIONAL
  evidence:
  - reference: PMID:23529829
    reference_title: "Skeletal clinical characteristics of osteogenesis imperfecta caused by haploinsufficiency mutations in COL1A1."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      Scoliosis was present in about 30% of pediatric patients but the Cobb
      angle was <30 degrees in all cases.
    explanation: >-
      Supports scoliosis as an occasional and usually mild spinal manifestation
      in pediatric type I OI.
- name: Hearing Impairment
  description: >
    Progressive hearing impairment usually begins in adulthood, with onset most
    often in the second to fourth decades.
  phenotype_term:
    preferred_term: Hearing impairment
    term:
      id: HP:0000365
      label: Hearing impairment
  evidence:
  - reference: PMID:11276328
    reference_title: "How common is hearing impairment in osteogenesis imperfecta?"
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      It was found that the most common age of onset was in the second, third
      and fourth decades of life. At the age of 50 approximately 50 per cent of
      the patients had symptoms of hearing impairment; over the next 20 years
      there was little further increase. Differences were shown between patients
      with different clinical types of osteogenesis imperfecta as delineated in
      the Sillence classification; hearing loss was significantly less common in
      the type IV disease than in the type I disorder.
    explanation: >-
      Large OI survey showing typical adult onset of hearing impairment and
      demonstrating that hearing loss is more common in type I than in type IV
      disease.
- name: Dentinogenesis Imperfecta
  description: >
    Dentinogenesis imperfecta can occur in a subset of children with
    osteogenesis imperfecta type I.
  phenotype_term:
    preferred_term: Dentinogenesis imperfecta
    term:
      id: HP:0000703
      label: Dentinogenesis imperfecta
  evidence:
  - reference: PMID:20384825
    reference_title: "Dentinogenesis imperfecta in children with osteogenesis imperfecta: a clinical and ultrastructural study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: >-
      RESULTS: A total of ten patients had abnormal discolourations referable
      to DI: four patients were affected by OI type I, three patients by OI
      type III, and three patients by OI type IV.
    explanation: >-
      Pediatric cohort directly documenting dentinogenesis imperfecta in
      children with type I OI.
diagnosis:
- name: Clinical and Molecular Diagnosis
  description: >-
    The diagnosis of osteogenesis imperfecta type I (now described in
    GeneReviews as classic non-deforming OI with blue sclerae) rests on the
    characteristic clinical and radiographic features of mild bone fragility
    with blue sclerae, and is confirmed by identification of a heterozygous
    COL1A1 null variant on molecular genetic testing.
  diagnosis_term:
    preferred_term: molecular genetic testing
    term:
      id: MAXO:0000533
      label: molecular genetic testing
  evidence:
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis of COL1A1/COL1A2-OI is established in a proband with clinical and radiographic manifestations of OI by identification of a heterozygous in COL1A1 or COL1A2 by molecular genetic testing."
    explanation: >-
      GeneReviews defines the combined clinical/radiographic plus molecular
      diagnostic criteria for COL1A1/COL1A2-related OI, which includes the mild
      type I (classic non-deforming) form.
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "classic non-deforming OI with blue sclerae (previously OI type I)"
    explanation: >-
      GeneReviews maps the legacy Sillence type I label to the modern
      descriptive nomenclature for the mild, non-deforming form.
- name: Multidisciplinary Surveillance
  description: >-
    Surveillance appropriate to OI severity includes serial bone-density
    assessment, hearing evaluation, dental review, and growth/spine monitoring.
  evidence:
  - reference: PMID:20301472
    reference_title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "DXA scans beginning at age five years with follow-up scan based on severity of OI, initial results, and pharmacologic treatment status."
    explanation: >-
      GeneReviews specifies bone-density surveillance as part of routine OI
      monitoring, tailored for mild type I to fracture history and treatment
      status.
treatments:
- name: Bisphosphonate Therapy
  description: >
    Bisphosphonate therapy is used clinically in the management of skeletal
    fragility in osteogenesis imperfecta, particularly in children.
  treatment_term:
    preferred_term: Bisphosphonate therapy
    term:
      id: MAXO:0000954
      label: bisphosphonate agent therapy
- name: Physical Therapy
  description: >
    Exercise and physical therapy to strengthen muscles and improve mobility
    while protecting fragile bones.
  treatment_term:
    preferred_term: Physical therapy
    term:
      id: MAXO:0000011
      label: physical therapy
- name: Fracture Management
  description: >
    Standard orthopedic management of fractures with appropriate immobilization.
  treatment_term:
    preferred_term: Orthopedic surgery
    term:
      id: MAXO:0000004
      label: surgical procedure
datasets:
references:
- reference: PMID:20301472
  title: "COL1A1- and COL1A2-Related Osteogenesis Imperfecta."
  tags:
  - GeneReviews
  findings: []
- reference: DOI:10.1007/s00223-024-01266-5
  title: Update on the Genetics of Osteogenesis Imperfecta
  findings: []
- reference: DOI:10.1210/endrev/bnab017
  title: 'Osteogenesis Imperfecta: Mechanisms and Signaling Pathways Connecting Classical
    and Rare OI Types'
  findings: []
- reference: DOI:10.1371/journal.pone.0309801
  title: Pleiotropic effects of a recessive Col1a2 mutation occurring in a mouse
    model of severe osteogenesis imperfecta
  findings: []
- reference: DOI:10.3390/jcm13123484
  title: 'Unraveling the Link of Altered TGFβ Signaling with Scoliotic Vertebral Malformations
    in Osteogenesis Imperfecta: A Comprehensive Review'
  findings: []

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References & Deep Research