TY - JOUR
T1 - Mutations in PIEZO2 Cause Gordon Syndrome, Marden-Walker Syndrome, and Distal Arthrogryposis Type 5
AU - McMillin, Margaret J.
AU - Beck, Anita E.
AU - Chong, Jessica X.
AU - Shively, Kathryn M.
AU - Buckingham, Kati J.
AU - Gildersleeve, Heidi I. S.
AU - Aracena, Mariana I.
AU - Aylsworth, Arthur S.
AU - Bitoun, Pierre
AU - Carey, John C.
AU - Clericuzio, Carol L.
AU - Crow, Yanick J.
AU - Curry, Cynthia J.
AU - Devriendt, Koenraad
AU - Everman, David B.
AU - Fryer, Alan
AU - Gibson, Kate
AU - Uzielli, Maria Luisa Giovannucci
AU - Graham, John M., Jr.
AU - Hall, Judith G.
AU - Hecht, Jacqueline T.
AU - Heidenreich, Randall A.
AU - Hurst, Jane A.
AU - Irani, Sarosh
AU - Krapels, Ingrid P. C.
AU - Leroy, Jules G.
AU - Mowat, David
AU - Plant, Gordon T.
AU - Robertson, Stephen P.
AU - Schorry, Elizabeth K.
AU - Scott, Richard H.
AU - Seaver, Laurie H.
AU - Sherr, Elliott
AU - Splitt, Miranda
AU - Stewart, Helen
AU - Stumpel, Constance
AU - Temel, Sehime G.
AU - Weaver, David D.
AU - Whiteford, Margo
AU - Williams, Marc S.
AU - Tabor, Holly K.
AU - Smith, Joshua D.
AU - Shendure, Jay
AU - Nickerson, Deborah A.
AU - University of Washington Center for Mendelian Genomics
AU - Bamshad, Michael J.
PY - 2014/5/1
Y1 - 2014/5/1
N2 - Gordon syndrome (GS), or distal arthrogyposis 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 mechano-sensitive 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 <0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.
AB - Gordon syndrome (GS), or distal arthrogyposis 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 mechano-sensitive 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 <0.0001). Collectively, although GS, DA5, and MWS have traditionally been considered separate disorders, our findings indicate that they are etiologically related and perhaps represent variable expressivity of the same condition.
U2 - 10.1016/j.ajhg.2014.03.015
DO - 10.1016/j.ajhg.2014.03.015
M3 - Article
C2 - 24726473
SN - 0002-9297
VL - 94
SP - 734
EP - 744
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -