A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation. (25th February 2015)

• Record Type: Journal Article
• Authors: Okubo, Mariko; Fujita, Atsushi; Saito, Yoshiaki; Komaki, Hirofumi; Ishiyama, Akihiko; Takeshita, Eri; Kojima, Emiko; Koichihara, Reiko; Saito, Takashi; Nakagawa, Eiji; Sugai, Kenji; Yamazaki, Hiroko; Kusaka, Kei; Tanaka, Hiroshi; Miyake, Noriko; Matsumoto, Naomichi; Sasaki, Masayuki
• Is Part Of: American journal of medical genetics. Volume 167:Number 5(2015:May)
• Page Start: 1100
• Page End: 1106
• Publication Date: 2015-02-25
• Subjects: Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.36881
• Languages: English
• ISSNs: 1552-4825

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ajmga36881-sec-0001" sec-type="section"> <p>Distal arthrogryposis (DA) encompasses a heterogeneous group of hereditary disorders with multiple congenital contractures predominant in the distal extremities. A total of 10 subtypes are proposed based on the pattern of contractures and association with extraarticular symptoms. DA5 is defined as a subtype with ptosis/oculomotor limitation. However, affected individuals have a variety of non‐ocular features as well. We report on a two‐generation family, including four affected individuals who all had congenital contractures of the distal joints, ptosis, restricted ocular movements, distinct facial appearance with deep‐set eyes, and shortening of the 1st and 5th toes. The proband and her affected mother had restrictive lung disease, a recently recognized syndromic component of DA5, while younger patients did not. The proband had metacarpal and metatarsal synostosis, and the mother showed excavation of the optic disk. Whole‐exome sequencing revealed a novel heterozygous mutation c.4456G&gt;C (p.A1486P) of <italic>PIEZO2. PIEZO2</italic> encodes a mechanosensitive ion channel, malfunction of which provides pleiotropic effects on joints, ocular muscles, lung function, and bone development. © 2015 Wiley Periodicals, Inc.</p> </sec> </abstract>