Protein-altering MYH3 variants are associated with a spectrum of phenotypes extending to spondylocarpotarsal synostosis syndrome.

Date publication

décembre 2016

Journal

European journal of human genetics : EJHG

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak , Dr CARAPITO Raphaël

Tous les auteurs :
Carapito R, Goldenberg A, Paul N, Pichot A, David A, Hamel A, Dumant-Forest C, Leroux J, Ory B, Isidor B, Bahram S

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/27381093

Résumé

Spondylocarpotarsal synostosis syndrome (SCT) is a rare Mendelian disorder (OMIM #272460) characterized by prenatal vertebral fusion, scoliosis, short stature and carpal and tarsal synostosis. SCT is typically known as an autosomal recessive disease caused by variants in the FLNB gene. The genetic basis of the rarer cases of vertical transmissions remains unknown. In two independent families with symptoms related to autosomal dominant SCT, we identified - by exome sequencing - two protein-altering variants in the embryonic myosin heavy chain 3 (MYH3) gene. As MYH3 variants are also associated with distal arthrogryposis (DA1, DA2A, DA2B) and autosomal dominant multiple pterygium syndromes (MPS), the present study expands the phenotypic spectrum of MYH3 variants to autosomal dominant SCT. Vertebral, carpal and tarsal fusions observed in both families further confirm that MYH3 plays a key role in skeletal development.

Référence

Eur. J. Hum. Genet.. 2016 Dec;24(12):1746-1751