title: A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation.
abstract: 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>C (p.A1486P) of PIEZO2. PIEZO2 encodes a mechanosensitive ion channel, malfunction of which provides pleiotropic effects on joints, ocular muscles, lung function, and bone development.
authors.affiliation: Department of Child Neurology, National Center of Neurology and Psychiatry, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Okubo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fujita
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Saito
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Komaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Ishiyama
authors.forename: Eri
authors.initials: E
authors.lastname: Takeshita
authors.forename: Emiko
authors.initials: E
authors.lastname: Kojima
authors.forename: Reiko
authors.initials: R
authors.lastname: Koichihara
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakagawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugai
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamazaki
authors.forename: Kei
authors.initials: K
authors.lastname: Kusaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Noriko
authors.initials: N
authors.lastname: Miyake
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sasaki
mesh_terms: D000293:Adolescent; D000328:Adult; D001176:Arthrogryposis / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D009135:Muscular Diseases / Q000235:genetics / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009900:Optic Nerve / Q000503:physiopathology*; D010375:Pedigree; D017422:Sequence Analysis, DNA; D013580:Synostosis / Q000235:genetics / Q000503:physiopathology
chemical_list: D007473:Ion Channels; C000589132:PIEZO2 protein, human
keywords: PIEZO2; distal arthrogryposis type 5; mechanosensitive ion channel; myopathy; optic nerve; restrictive lung disease; synostosis