Limb disorders

Gene: BHLHA9

Comment on mode of inheritance: Changing MOI back to biallelic only, as the duplication of this gene in SPLIT HAND AND FOOT MALFORMATION seems to be more of a susceptibility factor.

Created: 9 Dec 2018, 11:28 a.m.

In Gene2Phenotype this gene is also associated with SPLIT HAND AND FOOT MALFORMATION where there is a duplication of the gene. Mode of Inheritance is monoalleleic. PMID: 23790188 - by quantitive PCR a BHLHA9 duplication in 13 unrelated probands by qPCR, among 72 cases of ectrodactyly and/or long‐bone deficiency studied. Pedigrees often showed non‐penetrant individuals. 19 obligate carriers of the BHLHA9 duplication were asymptomatic (9 females and 10 males).
PMID: 22147889 report detailed analysis of 17 families with microduplicatiosn on duplication at 17p13.3. The minimal critical region encompasses the single gene, BHLHA9. Using quantitative real-time PCR to study affected and non-affected SHFLD family members they identified a high degree of non-penetrance. In those with duplications. 42 were affected but there were 40 unaffected carriers. More males (30/42) were affected than females (12/42). The authors suggest that this shows a non-Mendelian inheritance pattern with reduced recurrence risk and many mothers who are healthy carriers.

Created: 9 Sep 2018, 9:09 p.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. At least three variants reported

Created: 27 Jul 2016, 2:07 p.m.

Comment on phenotypes: One variant reported in Camptosynpolydactyly, complex 607539

Created: 27 Jul 2016, 2:06 p.m.

Green List (high evidence)

Tier 2

Created: 17 Jun 2016, 8:01 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Syndactyly, mesoaxial synostotic, with phalangeal reduction 609432

Variants in this GENE are reported as part of current diagnostic practice