Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5.

TitleMutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5.
Publication TypeJournal Article
Year of Publication2014
AuthorsMcMillin, MJ, Beck, AE, Chong, JX, Shively, KM, Buckingham, KJ, Gildersleeve, HIS, Aracena, MI, Aylsworth, AS, Bitoun, P, Carey, JC, Clericuzio, CL, Crow, YJ, Curry, CJ, Devriendt, K, Everman, DB, Fryer, A, Gibson, K, Uzielli, MLuisa Giov, Graham, JM, Hall, JG, Hecht, JT, Heidenreich, RA, Hurst, JA, Irani, S, Krapels, IPC, Leroy, JG, Mowat, D, Plant, GT, Robertson, SP, Schorry, EK, Scott, RH, Seaver, LH, Sherr, E, Splitt, M, Stewart, H, Stumpel, C, Temel, SG, Weaver, DD, Whiteford, M, Williams, MS, Tabor, HK, Smith, JD, Shendure, J, Nickerson, DA, Bamshad, MJ
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalAm J Hum Genet
Volume94
Issue5
Pagination734-44
Date Published2014 May 01
ISSN1537-6605
KeywordsAbnormalities, Multiple, Arachnodactyly, Arthrogryposis, Blepharophimosis, Child, Child, Preschool, Cleft Palate, Clubfoot, Connective Tissue Diseases, Contracture, Exome, Female, Hand Deformities, Congenital, Humans, Ion Channels, Male, Mutation, Ophthalmoplegia, Pedigree, Retinal Diseases
Abstract

Gordon syndrome (GS), or distal arthrogryposis type 3, is a rare, autosomal-dominant disorder characterized by cleft palate and congenital contractures of the hands and feet. Exome sequencing of five GS-affected families identified mutations in piezo-type mechanosensitive ion channel component 2 (PIEZO2) in each family. Sanger sequencing revealed PIEZO2 mutations in five of seven additional families studied (for a total of 10/12 [83%] individuals), and nine families had an identical c.8057G>A (p.Arg2686His) mutation. The phenotype of GS overlaps with distal arthrogryposis type 5 (DA5) and Marden-Walker syndrome (MWS). Using molecular inversion probes for targeted sequencing to screen PIEZO2, we found mutations in 24/29 (82%) DA5-affected families and one of two MWS-affected families. The presence of cleft palate was significantly associated with c.8057G>A (Fisher's exact test, adjusted p value

DOI10.1016/j.ajhg.2014.03.015
Alternate JournalAm. J. Hum. Genet.
PubMed ID24726473
PubMed Central IDPMC4067551
Grant ListU54 HG006493 / HG / NHGRI NIH HHS / United States
RC2 HG005608 / HG / NHGRI NIH HHS / United States
1R01HD048895 / HD / NICHD NIH HHS / United States
1RC2HG005608 / HG / NHGRI NIH HHS / United States
R00 HG004316 / HG / NHGRI NIH HHS / United States
K23 HD057331 / HD / NICHD NIH HHS / United States
R01 HD048895 / HD / NICHD NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States
5R000HG004316 / HG / NHGRI NIH HHS / United States
1U54HG006493 / HG / NHGRI NIH HHS / United States
5K23HD057331 / HD / NICHD NIH HHS / United States