Short Stature, Amelogenesis Imperfecta, and Skeletal Dysplasia with Scoliosis

1. Disease Information

Overview: Short Stature, Amelogenesis Imperfecta, and Skeletal Dysplasia with Scoliosis (SSASKS) is an ultra-rare autosomal recessive skeletal dysplasia first delineated in 2018. It is caused by biallelic loss-of-function variants in SLC10A7, encoding an orphan 10-transmembrane-domain Golgi/plasma-membrane transporter previously of unknown function. The disorder begins with pre- and postnatal growth failure and evolves into a multisystem phenotype dominated by disproportionate short stature, hypomineralized/hypoplastic amelogenesis imperfecta, progressive skeletal dysplasia with large-joint dislocations, and severe scoliosis, with variable facial dysmorphism, hearing impairment, and mild intellectual disability (Nature Communications 2018; OMIM #618363).

Mechanistically it is classified as a congenital disorder of glycosylation (CDG) — specifically "SLC10A7-CDG" — because loss of SLC10A7 disrupts Golgi calcium homeostasis, downstream glycosyltransferase activity, glycosaminoglycan (GAG)/proteoglycan biosynthesis, and post-Golgi glycoprotein trafficking, converging on a phenotype affecting bone, cartilage, and tooth enamel (PMID:34999954).

Key identifiers: - OMIM: #618363 (phenotype, SSASKS); 611459 (gene, SLC10A7) - Gene: SLC10A7 (HGNC:23088), chromosome 4q31.21 - Inheritance: Autosomal recessive - Suggested MONDO term: MONDO entity mapping to OMIM 618363 (curator should verify the exact MONDO CURIE via OLS/Monarch, as searches did not return a definitive standalone MONDO number distinct from the OMIM cross-reference) - Also known as:* SLC10A7-related skeletal dysplasia; SLC10A7-CDG; "skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects" (descriptive name from the founding paper)

Evidence base: This is a very rare, literature-derived (aggregated case-series) knowledge base — not EHR-derived. Only ~12–13 patients have been reported worldwide as of the most recent case report (2023), spanning six original families (Turkish, Iranian, Dutch) in the 2018 founding paper, plus subsequent single-family reports from France, Netherlands, and China (PMC10691085).

2. Etiology

Disease Causal Factors: SSASKS is purely genetic/monogenic — biallelic (homozygous or compound heterozygous) pathogenic variants in SLC10A7. No environmental, infectious, or acquired causal factors have been reported.

Genetic risk factors: - Consanguinity is a major risk factor: the founding cohort included four families from consanguineous unions in Turkey and Iran, plus two distantly related Dutch families (PMID:30082715). - Variant spectrum identified to date: - Two splice-site mutations (exons 9–10) - Missense: p.Leu74Pro (exon 3), p.Gly130Arg (exon 4), p.Pro303Leu (exon 11 — associated with a milder phenotype; PMID:31191616) - Nonsense: p.Gln172 (exon 7); p.Gly34 (exon 1, novel, first reported in a Han Chinese patient; PMC10691085) - Functional studies confirm these variants reduce SLC10A7 protein expression/stability at the plasma membrane and Golgi. - Genotype–phenotype correlation: The p.Pro303Leu missense variant, located near the C-terminus, is associated with a milder skeletal phenotype (growth retardation of −3SD vs. −4 to −10SD in other cases, absence of multiple joint dislocations), suggesting variant position and residual protein function modulate severity (PMC6546871).

Environmental/other risk factors: None established; the disease is fully genetically determined.

Protective factors: None reported in the literature.

Gene-environment interactions: Not applicable/not studied — no evidence of environmental modulation of expressivity.

3. Phenotypes

Skeletal/Growth (onset: prenatal/congenital, progressive)

• Disproportionate short stature — the cardinal feature, present in ~95% of reported cases, with birth length often <−3 SD and adult/childhood heights ranging from −3SD to as severe as −10SD in some patients. Suggested term: HP:0004322 (Short stature)
• Multiple large-joint dislocations with a characteristic "monkey wrench"/"Swedish key" femoral head appearance (radiographically shared with Desbuquois dysplasia) — HP:0001373 (Joint dislocation)
• Advanced carpal/tarsal bone ossification — HP:0006247
• Platyspondyly/abnormal vertebral bodies — HP:0000926
• Progressive scoliosis/kyphoscoliosis, present in ~80% of cases, often severe and requiring surgical intervention — HP:0002650 (Scoliosis)
• Genu valgum, short long bones, small epiphyses, horizontal acetabula — HP:0002857, HP:0003026
• Brachydactyly and progressive joint contractures in some patients — HP:0001156

Dental (essentially fully penetrant — 100%)

• Amelogenesis imperfecta, hypoplastic/hypomineralized type — thin (~80 μm vs. ~700 μm control), yellow-brown, rough-surfaced enamel — HP:0000705 (Abnormality of dental enamel) / HP:0009805 (hypoplastic amelogenesis imperfecta)
• Delayed tooth eruption (91.6%) — HP:0000684
• Oligodontia/hypodontia/tooth agenesis (88%) — HP:0000696

Craniofacial

• Facial dysmorphism — flat face, micro/retrognathia, microretrognathia, Pierre-Robin sequence in some cases — HP:0000271
• Ptosis, in individual case reports — HP:0000508

Sensory/Neurologic

• Moderate bilateral hearing impairment in a subset of patients — HP:0000407
• Mild intellectual disability/learning difficulties — variable, not universal — HP:0001256
• Optic nerve atrophy reported in at least one case — HP:0000648

Other

• Cardiac defects — aortic sinus dilation, patent foramen ovale reported in individual patients — HP:0004942
• Obesity noted in older patients in the founding cohort
• Whole-body edema (in the zebrafish model correlate; not consistently reported in humans)

Quality of life impact: Not formally studied with validated instruments (EQ-5D/SF-36); qualitatively, the disease imposes major cumulative burden from repeated orthopedic surgeries (documented case: 7 surgeries over 12 years for scoliosis management), chronic joint instability, and dental rehabilitation needs.

4. Genetic/Molecular Information

• Causal gene: SLC10A7 (HGNC:23088, OMIM 611459), chromosome 4q31.21, encoding a 10-transmembrane-domain protein of the SLC10 (sodium/bile acid cotransporter) family. Despite structural homology to bile-acid transporters, SLC10A7 shows no transport activity for canonical SLC10 substrates* and is classified as an "orphan carrier" (PMID:34999954).
• Variant classification: All reported variants are biallelic loss-of-function or hypomorphic (missense) — consistent with ACMG pathogenic/likely pathogenic — no VUS controversies reported to date given the small case series and strong functional validation.
• Variant types: Missense (p.Leu74Pro, p.Gly130Arg, p.Pro303Leu), nonsense (p.Gln172, p.Gly34), splice-site (exons 9–10).
• Allele frequency: Given the ultra-rare presentation (~12–13 reported cases worldwide, primarily from consanguineous unions), population database (gnomAD) frequencies for specific pathogenic alleles are expected to be exceedingly low or absent (no specific data returned in this search — should be verified directly in gnomAD/ClinVar during curation).
• Somatic vs. germline: Germline only — a classic recessive Mendelian disorder.
• Functional consequences: Loss-of-function/reduced protein expression at the Golgi/plasma membrane, leading to:
• Dysregulated intracellular (Golgi) calcium homeostasis — patient fibroblasts show significantly increased Ca²⁺ influx upon calcium challenge, and SLC10A7 has been separately characterized as "a novel negative regulator of intracellular calcium signaling" (PMID:32350310)
• Reduced heparan sulfate (GAG) biosynthesis (~2–2.5-fold reduction in Slc10a7−/− mouse cartilage and patient fibroblasts), with total GAG preserved via compensatory chondroitin sulfate synthesis
• Abnormal N-glycosylation — increased high-mannose glycans, glycans lacking GlcNAc, and decreased sialylated glycans on plasma glycoproteins (e.g., transferrin), plus mislocalized/defective post-Golgi glycoprotein transport (PMC10691085; HMG 2018, Ashikov et al.)
• Modifier genes: None identified.
• Epigenetic information: Not studied for this disorder.
• Chromosomal abnormalities: Not applicable — point/splice-site variants only, no reported CNVs.

5. Environmental Information

No environmental, lifestyle, or infectious contributing factors have been identified or are biologically plausible given the purely monogenic glycosylation/transporter mechanism. Not applicable to this entry.

6. Mechanism / Pathophysiology

Causal chain (upstream → downstream):

1. Trigger (molecular scale): Biallelic SLC10A7 loss-of-function variant → loss/reduction of functional SLC10A7 transporter at the Golgi and plasma membrane.
2. Golgi calcium dysregulation: SLC10A7 normally regulates intracellular (Golgi-lumen) Ca²⁺ homeostasis; its loss causes increased cytosolic/ER-store Ca²⁺ influx in patient fibroblasts. Suggested GO term: GO:0051480 (regulation of cytosolic calcium ion concentration); GO:0032468 (Golgi calcium ion homeostasis).
3. Downstream glycosylation defect: Golgi Ca²⁺ dysregulation impairs Ca²⁺-dependent glycosyltransferase activity, producing:
4. Congenital disorder of glycosylation (CDG) signature — abnormal N-glycan profiles on serum glycoproteins (increased high-mannose species, decreased sialylation) — GO:0006486 (protein glycosylation)
5. Reduced heparan sulfate GAG chain synthesis on proteoglycans in cartilage and fibroblasts — GO:0015012 (heparan sulfate proteoglycan biosynthetic process)
6. Defective post-Golgi trafficking of glycoproteins/proteoglycans to the extracellular matrix — GO:0006891 (intra-Golgi vesicle-mediated transport)
7. Tissue-level consequences (cellular/tissue scale):
8. Growth plate chondrocyte disorganization — thinned growth plates, disorganized proliferative/hypertrophic zones, reduced Safranin O (sulfated GAG) staining in Slc10a7−/− mouse cartilage
9. Ameloblast dysfunction — missing aprismatic enamel layer, enamel hypoplasia, due to disrupted secretory-pathway glycoprotein trafficking in ameloblasts
10. Osteoblast/matrix mineralization defect — zebrafish slc10a7 morphants show near-absent bone mineralization (Alizarin red staining), implicating a role in extracellular matrix mineralization via proteoglycan/glycoprotein delivery
11. Organismal-level phenotype: Growth plate and enamel matrix disruption → disproportionate short stature, brachyolmia-type skeletal dysplasia, joint laxity/dislocation (proteoglycan-dependent cartilage/ligament integrity), and amelogenesis imperfecta; spinal deformity progresses to severe scoliosis.

Cell types involved: Growth-plate chondrocytes (CL:0000138 chondrocyte), ameloblasts (CL:0000414), osteoblasts (CL:0000062), dermal fibroblasts (CL:0000057, used as the patient-derived disease model).

Molecular profiling evidence: - Glycomics: Abnormal serum/plasma N-glycan and O-glycan profiles in patients (isoelectric focusing of transferrin showing hypoglycosylation pattern consistent with CDG type II). - No transcriptomic, proteomic, or single-cell datasets specific to this ultra-rare disease were identified in this search; the mechanistic work has been carried out primarily via targeted biochemical assays (Ca²⁺ imaging, GAG quantification, glycan mass spectrometry) in patient fibroblasts and animal models rather than omics screens.

7. Anatomical Structures Affected

Organ/system level: - Skeletal system (primary) — long bones, vertebral column, joints, cranium (UBERON:0001434 skeletal system) - Dentition — tooth enamel specifically (UBERON:0001754 tooth enamel) - Craniofacial skeleton (UBERON:0001456) - Auditory system (secondary — hearing impairment) (UBERON:0001690 ear) - Cardiovascular system (secondary, in some patients — aortic root/valve) (UBERON:0002012 aorta) - Central nervous system (secondary — optic nerve, mild cognitive involvement) (UBERON:0001784 optic nerve)

Tissue/cell level: - Growth-plate cartilage (UBERON:0002514 epiphyseal cartilage) — chondrocytes (CL:0000138) - Enamel organ/ameloblasts (CL:0000414) - Bone matrix/osteoblasts (CL:0000062) - Synovial joint capsule/ligament — connective tissue affected by GAG deficiency (UBERON:0000982 ligament)

Subcellular level: - Golgi apparatus (GO:0005794) — primary site of SLC10A7 localization and dysfunction - Plasma membrane (GO:0005886) — SLC10A7's other reported localization - Secretory pathway vesicles (GO:0030133)

Localization: Bilateral/symmetric skeletal involvement; scoliosis typically thoracolumbar; dental involvement affects both primary and permanent dentition diffusely.

8. Temporal Development

• Onset: Congenital/prenatal — growth restriction is detectable pre- and postnatally (birth length often <−3SD; one reported case had birth height of 42 cm). Amelogenesis imperfecta is evident with primary tooth eruption.
• Onset pattern: Insidious, with progressive worsening through childhood.
• Progression: Skeletal dysplasia and scoliosis are progressive — the documented surgical case shows scoliosis requiring intervention beginning at age 3.5 years and continuing through age 14.2 years (growth-rod placement → lengthening procedures → dual-rod conversion → definitive fusion). Joint contractures are also described as progressive.
• Disease course pattern: Chronic, progressive, non-relapsing/non-remitting (no spontaneous remission reported).
• Critical periods: Early childhood is a critical intervention window for scoliosis management (growth-friendly rod systems) to preserve spinal/thoracic growth before definitive fusion at skeletal maturity.
• Disease duration: Lifelong; no evidence this is self-limited. Life expectancy has not been formally quantified in the literature but no early mortality has been reported in the ~12 documented cases.

9. Inheritance and Population

Epidemiology: - Prevalence: Ultra-rare; only ~12–13 cases described in the world literature to date across 3 primary publications (2018 founding cohort of 6 patients from 4 families; 2019 single French case; 2023 single Chinese case), plus at least one additional 2021 case (splicing variant, brachyolmia with AI). No formal prevalence estimate (e.g., per 100,000) has been published — likely falls in the "<1/1,000,000" (ultra-rare) band. - Incidence: Not calculable given the extremely small reported case count.

Inheritance pattern: Autosomal recessive (AR). Penetrance: Appears complete for the core triad (short stature, AI, skeletal dysplasia) among reported homozygous/compound heterozygous individuals, though severity is variable. Expressivity: Variable — genotype-correlated (e.g., the p.Pro303Leu missense case showed a substantially milder skeletal phenotype than nonsense/splice-site cases). Founder effects: Multiple independent founder-type events plausible given consanguineous Turkish and Iranian families in the original cohort, plus two distantly related Dutch families sharing ancestry. Consanguinity: A major contributing factor — 4 of the 6 original index families were from consanguineous unions. Carrier frequency: Not established (too rare for population-level carrier frequency data).

Population demographics: - Cases reported from Turkey, Iran, the Netherlands, France, and China — no clear single ethnic predominance, consistent with a pan-ethnic ultra-rare AR disorder that surfaces preferentially in consanguineous populations. - Sex ratio: No skewing reported (autosomal gene). - Age distribution: All reported cases are pediatric/adolescent at diagnosis given the congenital onset.

10. Diagnostics

Clinical tests: - Imaging (primary diagnostic modality): Skeletal radiographic survey showing platyspondyly, "Swedish key"/monkey-wrench femoral heads, advanced carpal/tarsal bone age, multiple large-joint dislocations, and progressive scoliosis on spine films. Suggested RadLex/imaging term: skeletal survey for skeletal dysplasia. - Dental examination: Clinical and radiographic assessment of enamel thickness/mineralization (enamel ~80 μm vs. ~700 μm normal in one measured case). - Biochemical/glycomics: Serum transferrin isoelectric focusing / N-glycan mass spectrometry showing a CDG type II-like abnormal glycosylation pattern (increased high-mannose glycans, decreased sialylation) — a distinguishing biomarker supporting the CDG mechanism. - Audiometry: For hearing impairment assessment. - Ophthalmologic exam: For optic nerve atrophy screening in symptomatic patients. - Echocardiography: To screen for aortic root dilation/cardiac anomalies given at least one reported case with aortic sinus dilation and PFO.

Genetic testing: - Gene panel/exome sequencing is the diagnostic approach of choice — all reported cases were solved via whole-exome sequencing given the absence of a prior clinical gestalt pointing specifically to SLC10A7 (initial presentations often resembled Desbuquois dysplasia or other multiple-dislocation skeletal dysplasias). - Single-gene Sanger confirmation of SLC10A7 variants in proband and segregation testing in parents (both heterozygous carriers in consanguineous families) is standard follow-up. - No chromosomal microarray, karyotype, or mitochondrial DNA testing is relevant (single-gene AR point/splice variants only).

Clinical/differential diagnosis: Because the "monkey wrench"/"Swedish key" femoral appearance and advanced carpal ossification overlap radiographically with the Desbuquois dysplasia spectrum (multiple-dislocation group of chondrodysplasias, itself associated with CANT1 and XYLT1 — also glycosylation/proteoglycan pathway genes), SSASKS should be differentiated from: - Desbuquois dysplasia 1/2 (CANT1, XYLT1) — OMIM #251450 - Geleophysic dysplasia (ADAMTSL2, FBN1, LTBP3) — a related but molecularly and phenotypically distinct entity - LTBP3-related "Dental Anomalies and Short Stature" (DASS, OMIM #601216) — an important, easily confused related disorder: LTBP3 biallelic variants cause brachyolmia with amelogenesis imperfecta and short stature, with cardiovascular complications (aortic aneurysm, mitral valve prolapse) as a more prominent feature; distinguishing molecular testing is essential since clinical overlap (short stature + AI + skeletal dysplasia + scoliosis) is substantial. - Other multiple-dislocation/AI-associated dysplasias.

The single most consistent distinguishing clinical clue across the literature is: "AI is the key feature indicative of SLC10A7 mutations in patients with skeletal dysplasia" — i.e., near-100% penetrant, severe hypomineralized amelogenesis imperfecta in combination with a multiple-dislocation skeletal dysplasia should trigger SLC10A7 testing (PMC6546871).

Screening: No population or newborn screening program exists (or is warranted) given the ultra-rare frequency; diagnosis is case-by-case via clinical suspicion + exome sequencing.

11. Outcome/Prognosis

• Survival/mortality: No deaths have been reported among the ~12–13 documented cases; formal survival statistics do not exist given the small numbers.
• Morbidity: Substantial — driven by progressive scoliosis (requiring multi-stage surgical correction across childhood/adolescence), joint dislocations/contractures affecting mobility, and dental rehabilitation needs due to severe enamel loss.
• Disease course: Chronic and progressive through childhood; the well-documented surgical case achieved a favorable final Cobb angle (16.3°) after a 12-year, 7-surgery growth-friendly-rod-to-fusion protocol, suggesting that with aggressive orthopedic management, functional spinal outcomes can be reasonably favorable.
• Complications: Progressive scoliosis, chronic joint instability/dislocation, hearing loss, dental complications (oligodontia, enamel loss requiring restorative dentistry), and in a subset, cardiac (aortic root dilation) and ophthalmologic (optic atrophy) complications.
• Prognostic factors: Variant type/location appears prognostic — missense variants near the C-terminus (e.g., p.Pro303Leu) are associated with a milder phenotype than nonsense/splice-site null alleles, which produce more severe growth failure and more extensive joint dislocation.
• Quality of life: Not formally measured with validated QOL instruments in the literature to date.

12. Treatment

There is no disease-modifying or gene-specific therapy for SSASKS/SLC10A7-CDG; management is entirely symptomatic/supportive and multidisciplinary.

Surgical/interventional (primary management for the skeletal phenotype): - Growth-friendly spinal instrumentation (single-side growth rods progressing to dual-rod systems with expanded screw fixation) for progressive early-onset scoliosis, followed by definitive spinal fusion at skeletal maturity — documented in detail in the 2023 case report (7 procedures over 12 years, from age 3.5 to 14.2 years). Suggested NCIT term: NCIT:C15329 (Surgical Procedure); more specifically, spinal fusion/instrumentation. - Orthopedic management of large-joint dislocations (surveillance, bracing, and surgical reduction/stabilization as needed) — NCIT:C16186 (Orthopedic Surgical Procedure).

Dental/restorative: - Restorative dental care for amelogenesis imperfecta — crowns, restorative bonding, or prosthodontic rehabilitation for severely hypomineralized/hypoplastic enamel; management of oligodontia (implants/prosthetics) — NCIT:C15329 (Surgical/dental procedure) as broad category; no specific NCIT dental-restoration term identified in this search.

Supportive care: - Audiologic support (hearing aids) for moderate hearing impairment — NCIT:C15747 (Supportive Care). - Physical/occupational therapy for joint contractures and mobility — NCIT:C15302 (Physical Therapy). - Cardiology follow-up (echocardiographic surveillance) for patients with aortic root involvement. - Genetic counseling for affected families, given AR inheritance and elevated recurrence risk (25%) in future pregnancies, particularly relevant in consanguineous populations — NCIT:C15240 (Genetic Counseling).

Experimental/pharmacotherapy: No clinical trials (ClinicalTrials.gov) or investigational drug therapies specific to SLC10A7-CDG were identified in this search. Given the CDG mechanism (defective glycosylation via Golgi Ca²⁺ dysregulation), this disorder is mechanistically distinct from the classical PMM2-CDG/mannose-supplementation-responsive CDGs, and no analogous small-molecule or dietary intervention has been proposed in the literature reviewed.

Treatment outcomes: The single well-documented surgical case achieved good radiographic correction (final Cobb angle 16.3°) with "no implant complications," suggesting growth-friendly instrumentation is an effective, if burdensome, strategy for the scoliosis component.

13. Prevention

• Primary prevention: Not applicable in the population sense; the only actionable prevention lever is genetic counseling and carrier testing in families with a known proband, particularly in consanguineous populations, to inform reproductive decision-making (prenatal diagnosis or preimplantation genetic testing for known familial SLC10A7 variants).
• Secondary prevention: Early clinical recognition (short stature + amelogenesis imperfecta + skeletal dysplasia triad) followed by prompt genetic diagnosis can enable earlier orthopedic surveillance and growth-friendly spinal intervention before scoliosis becomes severe.
• Tertiary prevention: Multidisciplinary surveillance (orthopedic, dental, audiologic, cardiac, ophthalmologic) to detect and manage complications early.
• Screening: No population-level newborn or carrier screening program exists given the extreme rarity; cascade testing within affected families is the practical approach.
• Public health/environmental interventions: Not applicable — purely monogenic disorder with no environmental modifiers.

14. Other Species / Natural Disease

No naturally occurring veterinary cases of SLC10A7-related disease have been reported in companion animals or wildlife (this appears to be an engineered/induced model space only — see Model Organisms below). No OMIA (Online Mendelian Inheritance in Animals) entries or veterinary case series were identified in this search.

15. Model Organisms

Mouse (Slc10a7−/−)

• Type: Genetic knockout, constitutive.
• Phenotype recapitulation — high fidelity:
• Shortened long bones and growth retardation (measurable at birth and at 8 weeks)
• Growth plate disorganization: markedly thinned growth plates with disorganized proliferative/hypertrophic chondrocyte zones
• Altered long-bone morphology matching the human "Swedish key" femoral appearance
• Tooth enamel anomalies including missing aprismatic enamel layer and enamel hypoplasia
• Reduced Safranin O staining (decreased sulfated GAG content) in cartilage, mechanistically linking to the ~2–2.5-fold reduction in heparan sulfate measured biochemically
• Source: PMID:30082715 (Dubail et al., Nature Communications 2018)
• Limitations: Not explicitly detailed in the sources reviewed, but as a constitutive null it cannot dissect tissue-specific/temporal requirements for SLC10A7.

Zebrafish (slc10a7 morpholino knockdown)

• Type: Morpholino-based transient knockdown (induced model).
• Phenotype:
• Dose-dependent severity: low-dose morpholino → mild skeletal/craniofacial defects; high-dose (12 ng/nl) → severe phenotype with whole-body edema, reduced head/eye size, curled body
• Cartilage/craniofacial malformation (bent-down jaw cartilage) on Alcian blue staining
• Near-absent bone mineralization on Alizarin red staining at high knockdown doses
• Source: Ashikov et al., Human Molecular Genetics 2018 — "Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation"
• Applications: Used to functionally validate patient-derived variants and to study the glycosylation/bone-mineralization mechanism in vivo.
• Limitations: Morpholino knockdown is transient/dose-dependent rather than a stable genetic model, and severe phenotypes (edema, curled body) may reflect broader developmental toxicity beyond the specific human skeletal/dental phenotype.

Patient-derived fibroblasts (in vitro, human)

• Used extensively to demonstrate increased Ca²⁺ influx upon calcium challenge, reduced heparan sulfate synthesis, and abnormal N-glycan profiles — directly bridging the mouse/zebrafish mechanistic data to human disease biology.

Resource note: No entries for SLC10A7 knockout mice were located in this search under standard identifiers (MGI, IMPC) — the model described in Dubail et al. 2018 appears to be a custom-generated line rather than a repository-deposited allele; this should be confirmed against MGI/IMPC directly during curation.

Summary of Key Ontology Term Suggestions for Curation

Important Curation Caveat

Do not confuse SSASKS (SLC10A7, OMIM #618363) with the phenotypically overlapping LTBP3-related disorder "Dental Anomalies and Short Stature" (DASS, OMIM #601216, also called brachyolmia with amelogenesis imperfecta). Both present with short stature + amelogenesis imperfecta + skeletal dysplasia/scoliosis, but they are molecularly and mechanistically distinct: SLC10A7 disease is a Golgi-calcium/glycosylation defect (GAG biosynthesis), while LTBP3 disease involves dysregulated TGF-β signaling and carries a more prominent cardiovascular phenotype (thoracic aortic aneurysm/dissection, mitral valve prolapse). Early web/AI searches for this exact title can misattribute the gene to LTBP3 — this is a named-entity-confusion risk given the near-identical clinical description; the correct causal gene for the title exactly as given ("Short Stature, Amelogenesis Imperfecta, and Skeletal Dysplasia with Scoliosis") is SLC10A7, per OMIM #618363.

Sources

• OMIM #618363 — SHORT STATURE, AMELOGENESIS IMPERFECTA, AND SKELETAL DYSPLASIA WITH SCOLIOSIS; SSASKS
• OMIM *611459 — SLC10A7
• OMIM #601216 — DENTAL ANOMALIES AND SHORT STATURE; DASS (LTBP3, related/differential disorder)
• Dubail J, et al. "SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects." Nat Commun. 2018. PMID:30082715 / PMC6078967
• Ashikov A, et al. "Integrating glycomics and genomics uncovers SLC10A7 as essential factor for bone mineralization by regulating post-Golgi protein transport and glycosylation." Hum Mol Genet. 2018. Oxford Academic
• "A New SLC10A7 Homozygous Missense Mutation Responsible for a Milder Phenotype of Skeletal Dysplasia With Amelogenesis Imperfecta." Front Genet. 2019. PMID:31191616 / PMC6546871
• "SLC10A7, an orphan member of the SLC10 family involved in congenital disorders of glycosylation." 2021. PMID:34999954
• "The orphan solute carrier SLC10A7 is a novel negative regulator of intracellular calcium signaling." PMID:32350310
• "Identification of novel homozygous nonsense SLC10A7 variant causing short stature, amelogenesis imperfecta, and skeletal dysplasia with scoliosis and surgical management of spine." Orphanet J Rare Dis. 2023. PMC10691085
• "A Rare Case of Brachyolmia with Amelogenesis Imperfecta Caused by a New Pathogenic Splicing Variant in LTBP3." Genes (Basel). 2021. PMC8470690
• GeneCards: SLC10A7

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