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- PMID: 24726473
- UKPMCID: 24726473
- DOI: 10.1016/j.ajhg.2014.03.015
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Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5.
McMillin, Margaret J; Beck, Anita E; Chong, Jessica X; Shively, Kathryn M; Buckingham, Kati J; Gildersleeve, Heidi I S; Aracena, Mariana I; Aylsworth, Arthur S; Bitoun, Pierre; Carey, John C; Clericuzio, Carol L; Crow, Yanick J; Curry, Cynthia J; Devriendt, Koenraad; Everman, David B; Fryer, Alan; Gibson, Kate; Giovannucci Uzielli, Maria Luisa; Graham, John M; Hall, Judith G; Hecht, Jacqueline T; Heidenreich, Randall A; Hurst, Jane A; Irani, Sarosh; Krapels, Ingrid P C; Leroy, Jules G; Mowat, David; Plant, Gordon T; Robertson, Stephen P; Schorry, Elizabeth K; Scott, Richard H; Seaver, Laurie H; Sherr, Elliott; Splitt, Miranda; Stewart, Helen; Stumpel, Constance; Temel, Sehime G; Weaver, David D; Whiteford, Margo; Williams, Marc S; Tabor, Holly K; Smith, Joshua D; Shendure, Jay; Nickerson, Deborah A; ; Bamshad, Michael J
American journal of human genetics. 2014;94(5):734-44.
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Full-text held externally
- PMID: 24726473
- UKPMCID: 24726473
- DOI: 10.1016/j.ajhg.2014.03.015
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 < 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.
Bibliographic metadata
- McMillin, Margaret J
- Beck, Anita E
- Chong, Jessica X
- Shively, Kathryn M
- Buckingham, Kati J
- Gildersleeve, Heidi I S
- Aracena, Mariana I
- Aylsworth, Arthur S
- Bitoun, Pierre
- Carey, John C
- Clericuzio, Carol L
- Crow, Yanick J
- Curry, Cynthia J
- Devriendt, Koenraad
- Everman, David B
- Fryer, Alan
- Gibson, Kate
- Giovannucci Uzielli, Maria Luisa
- Graham, John M
- Hall, Judith G
- Hecht, Jacqueline T
- Heidenreich, Randall A
- Hurst, Jane A
- Irani, Sarosh
- Krapels, Ingrid P C
- Leroy, Jules G
- Mowat, David
- Plant, Gordon T
- Robertson, Stephen P
- Schorry, Elizabeth K
- Scott, Richard H
- Seaver, Laurie H
- Sherr, Elliott
- Splitt, Miranda
- Stewart, Helen
- Stumpel, Constance
- Temel, Sehime G
- Weaver, David D
- Whiteford, Margo
- Williams, Marc S
- Tabor, Holly K
- Smith, Joshua D
- Shendure, Jay
- Nickerson, Deborah A
- Bamshad, Michael J