| Domain | Key findings | Quantitative details | Evidence level | Citation |
|---|---|---|---|---|
| Identity / identifier | Disease resolved as **alopecia-mental retardation syndrome 1 (APMR1)**, a very rare autosomal recessive condition mapped to **chromosome 3q26.33-q27.3**; characterized by alopecia with intellectual disability. OMIM given as **203650**. | Single disease entity discussed in one primary molecular report; linkage region reported as **17 Mb** on chr3. | Human clinical / gene-mapping | (pqac-00000002, pqac-00000001) |
| Gene and variant | Candidate causal gene is **AHSG** (*alpha-2-HS-glycoprotein*; fetuin-A; OMIM **138680**). Reported disease-associated variant: **c.950G>A (p.Arg317His)** in **exon 7**; dbSNP **rs201849460**. | Variant genomic position reported as **chr3:186338565**; rarity in ExAC reported as **MAF 0.0008%**. In silico scores: MutationTaster **0.95**, PolyPhen **0.99**, SIFT **0.0**. | Human segregation + computational | (pqac-00000002, pqac-00000003) |
| Inheritance / family | Inheritance is consistent with **autosomal recessive** transmission in a **large consanguineous Iranian family**. Variant segregated with disease. | **7 affected homozygous** individuals; **7 unaffected** relatives were heterozygous or homozygous reference; segregation significance reported as **chi-square P=0.01**. | Human segregation | (pqac-00000002, pqac-00000001, pqac-00000003) |
| Phenotype and patient counts | Core phenotype is **alopecia** plus **intellectual disability**. Hair loss may be **complete or partial**. APMR1 is described in 2024 context as having **mild-to-moderate ID**; developmental delay and epilepsy have been noted in APMR1 generally, but were not individually detailed in the extracted 2017 family table. | **7 affected** relatives total; ages explicitly visible for 7 individuals: **3Y, 4Y, 14Y, 17Y, 21Y, 23Y, 24Y**; sexes: **4 male, 3 female**; alopecia pattern among listed individuals: **3 complete, 4 partial**; IQ range **40-54**. | Human clinical observation | (pqac-00000006, pqac-00000005, pqac-00000011) |
| Functional evidence | AHSG/fetuin-A is implicated in **protein processing/post-translational modification**, **BMP/TGF-beta antagonism**, **keratinocyte migration**, and possible **brain developmental** roles. The APMR1 variant lies in the protein processing region and is predicted to disrupt a phosphorylation motif near **Thr319**; patient serum AHSG showed altered migration on SDS-PAGE. | Predicted loss/change of kinase recognition around **p.Thr319** with probabilities reported in one analysis as **0.96-0.74** for **PKA/DMPK/AUR** kinases; western blot showed **two bands in affected** versus **single bands in unaffected** controls. | In vitro / biochemical + computational | (pqac-00000001, pqac-00000003, pqac-00000000, pqac-00000009) |
| Diagnosis | No disease-specific standardized diagnostic criteria were identified. Current practical diagnosis depends on recognizing the phenotype and confirming **biallelic AHSG variation**, typically via **whole-exome sequencing** or other molecular testing. Broader ichthyosis/alopecia-neurodevelopmental literature supports NGS for rare syndromic differential diagnosis. | In a syndromic/non-syndromic ichthyosis cohort, NGS achieved a molecular diagnosis in **53/64 patients (82.8%)**, illustrating utility of panel/WES approaches for overlapping phenotypes. | Human diagnostic practice / extrapolated rare-disease genomics | (pqac-00000002, pqac-00000011) |
| Treatment / trials | **No disease-specific therapy** or management guideline for APMR1 was found in the retrieved evidence. Management is therefore presumed **supportive and multidisciplinary** (developmental, neurologic, dermatologic, rehabilitation, genetic counseling) rather than disease-modifying. **No relevant interventional clinical trials** were retrieved. | **0 relevant trials found** in the searched trial results. | Evidence gap / no active trial evidence retrieved | (pqac-00000006) |
| Major evidence gaps | Evidence base is extremely limited: one genetically resolved family, sparse natural-history data, no prevalence/incidence estimates, no penetrance estimates, no standardized diagnostic criteria, no biomarker validation, no disease-specific therapy, and no direct APMR1 animal model identified. Existing animal evidence for **AHSG** is indirect and comes from other phenotypes involving fetuin-A deficiency. | Human molecular evidence currently rests mainly on **1 family / 7 affected individuals**; indirect AHSG biology from knockout animals links fetuin-A deficiency to mineralization and bone phenotypes rather than a fully recapitulated APMR1 syndrome. | Animal indirect + evidence gap | (pqac-00000002, pqac-00000007, pqac-00000010) |


*Table: This table summarizes the strongest currently available evidence for alopecia-mental retardation syndrome 1 (APMR1), including identifiers, AHSG variant data, family segregation, phenotype counts, functional findings, and the major unresolved gaps. It is useful for rapidly distinguishing established human evidence from indirect mechanistic or animal evidence.*