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Distal arthrogryposis type 5 and PIEZO2 novel variant in a Canadian family
Author(s) -
ZapataAldana Eugenio,
AlMobarak Sulaiman B.,
Karp Natalya,
Campbell Craig
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61143
Subject(s) - arthrogryposis , phenotype , genetics , biology , muscle contracture , genetic counseling , gene , anatomy
The group of distal arthrogryposis (DA) disorders is characterized by congenital contractures of the distal joints. In most instances, these are genetic disorders are inherited in an autosomal dominant fashion; however, there is wide genetic and phenotypic spectrum. Distal arthrogryposis type 5 (DA5) is clinically characterized by short stature, deep‐set eyes, ptosis, ophthalmoplegia, triangular facies, restrictive pulmonary function, and “firm” muscles. DA5 is produced by a gain‐of‐function mutations in PIEZO2 gene , encoding for an ion‐channel required to convert mechanical stimulus to biological signals in mammals essential to proprioception. Heterozygous mutations in PIEZO2 may lead to other phenotypes like Gordon Syndrome and Marden Walker syndrome. In this report, we present a 3‐generation family affected with DA5, who all carry a variant of unknown clinical significance c.8068A>C (p.Ser2690Arg) in the PIEZO2 gene. DA5 is a very rare condition with less than 20 cases previously reported. Our report expands the phenotype and contributes to evidence of this variant's pathogenicity.