Curation HFG HOXA13-II
3 + 2.5 = 5.5 / 18
Genetic evidence
Total: 3
Category | Type | Citation | Score | Details |
|---|---|---|---|---|
Singular Evidence | Probands | 1.5 | One six-generation family with 27 affected individuals and atypical HFGS carried a heterozygous 18 bp duplication in the second HOXA13 polyalanine tract (+6 alanines); the variant was absent from 100 Swedish controls. | |
Collective Evidence | Segregation | 1.5 | Genome-wide linkage mapped the trait to chromosome 7p with maximum LOD 6.70 at θ=0 for D7S503; the HOXA13-II duplication was observed in all available affected family members, with one apparently unaffected carrier noted. |
Experimental evidence
Total: 2.5
Category | Type | Citation | Score | Details |
|---|---|---|---|---|
Function | Regulatory impact | 0.5 | Gene-level support for HOXA13 polyalanine expansion mechanisms, including reduced protein abundance/degradation and possible dominant-negative effects | |
Models | Non-human model organism | 2 | Gene-level, not HFG-II-specific: engineered Hoxa13 tract-III polyalanine-expansion mice (Hoxa13Ala28) showed limb phenotypes indistinguishable from Hoxa13 null mice and no homozygote survival to birth, supporting loss of function for HOXA13 polyalanine expansions. This evidence is not specific to tract-II, but supports the gene and the effect of polyalanine expansions in the gene. |