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

Margaret J. McMillin; Anita E. Beck; Jessica X. Chong; Kathryn M. Shively; Kati J. Buckingham; Heidi I S Gildersleeve; Mariana I. Aracena; Arthur S. Aylsworth; Pierre Bitoun; John C. Carey; Carol L. Clericuzio; Yanick J. Crow; Cynthia J. Curry; Koenraad Devriendt; David B. Everman; Alan Fryer; Kate Gibson; Maria Luisa Giovannucci Uzielli; John M. Graham; Judith G. Hall; Jacqueline T. Hecht; Randall A. Heidenreich; Jane A. Hurst; Sarosh Irani; Ingrid P C Krapels; Jules G. Leroy; David Mowat; Gordon T. Plant; Stephen P. Robertson; Elizabeth K. Schorry; Richard H. Scott; Laurie H. Seaver; Elliott Sherr; Miranda Splitt; Helen Stewart; Constance Stumpel; Sehime G. Temel; David D. Weaver; Margo Whiteford; Marc S. Williams; Holly K. Tabor; Joshua D. Smith; Jay Shendure; Deborah A. Nickerson; Michael J. Bamshad

doi:10.1016/j.ajhg.2014.03.015

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

Margaret J. McMillin, Anita E. Beck, Jessica X. Chong, Kathryn M. Shively, Kati J. Buckingham, Heidi I S Gildersleeve, Mariana I. Aracena, Arthur S. Aylsworth, Pierre Bitoun, John C. Carey, Carol L. Clericuzio, Yanick J. Crow, Cynthia J. Curry, Koenraad Devriendt, David B. Everman, Alan Fryer, Kate Gibson, Maria Luisa Giovannucci Uzielli, John M. Graham, Judith G. HallJacqueline T. Hecht, Randall A. Heidenreich, Jane A. Hurst, Sarosh Irani, Ingrid P C Krapels, Jules G. Leroy, David Mowat, Gordon T. Plant, Stephen P. Robertson, Elizabeth K. Schorry, Richard H. Scott, Laurie H. Seaver, Elliott Sherr, Miranda Splitt, Helen Stewart, Constance Stumpel, Sehime G. Temel, David D. Weaver, Margo Whiteford, Marc S. Williams, Holly K. Tabor, Joshua D. Smith, Jay Shendure, Deborah A. Nickerson, Michael J. Bamshad

Research output: Contribution to journal › Article › peer-review

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. © 2014 The American Society of Human Genetics.

Original language	English
Pages (from-to)	734-744
Number of pages	10
Journal	American Journal of Human Genetics
Volume	94
Issue number	5
DOIs	https://doi.org/10.1016/j.ajhg.2014.03.015
Publication status	Published - 1 May 2014

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McMillin, M. J., Beck, A. E., Chong, J. X., Shively, K. M., Buckingham, K. J., Gildersleeve, H. I. S., Aracena, M. I., Aylsworth, A. S., Bitoun, P., Carey, J. C., Clericuzio, C. L., Crow, Y. J., Curry, C. J., Devriendt, K., Everman, D. B., Fryer, A., Gibson, K., Giovannucci Uzielli, M. L., Graham, J. M., ... Bamshad, M. J. (2014). Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5. American Journal of Human Genetics, 94(5), 734-744. https://doi.org/10.1016/j.ajhg.2014.03.015

@article{46995d9db28b45da8d205164d759c4d1,

title = "Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5",

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. {\textcopyright} 2014 The American Society of Human Genetics.",

author = "McMillin, {Margaret J.} and Beck, {Anita E.} and Chong, {Jessica X.} and Shively, {Kathryn M.} and Buckingham, {Kati J.} and Gildersleeve, {Heidi I S} and Aracena, {Mariana I.} and Aylsworth, {Arthur S.} and Pierre Bitoun and Carey, {John C.} and Clericuzio, {Carol L.} and Crow, {Yanick J.} and Curry, {Cynthia J.} and Koenraad Devriendt and Everman, {David B.} and Alan Fryer and Kate Gibson and {Giovannucci Uzielli}, {Maria Luisa} and Graham, {John M.} and Hall, {Judith G.} and Hecht, {Jacqueline T.} and Heidenreich, {Randall A.} and Hurst, {Jane A.} and Sarosh Irani and Krapels, {Ingrid P C} and Leroy, {Jules G.} and David Mowat and Plant, {Gordon T.} and Robertson, {Stephen P.} and Schorry, {Elizabeth K.} and Scott, {Richard H.} and Seaver, {Laurie H.} and Elliott Sherr and Miranda Splitt and Helen Stewart and Constance Stumpel and Temel, {Sehime G.} and Weaver, {David D.} and Margo Whiteford and Williams, {Marc S.} and Tabor, {Holly K.} and Smith, {Joshua D.} and Jay Shendure and Nickerson, {Deborah A.} and Bamshad, {Michael J.}",

note = "1R01HD048895, NICHD NIH HHS, United States1RC2HG005608, NHGRI NIH HHS, United States1U54HG006493, NHGRI NIH HHS, United States5K23HD057331, NICHD NIH HHS, United States5R000HG004316, NHGRI NIH HHS, United States",

year = "2014",

month = may,

day = "1",

doi = "10.1016/j.ajhg.2014.03.015",

language = "English",

volume = "94",

pages = "734--744",

journal = "American Journal of Human Genetics",

issn = "0002-9297",

publisher = "Cell Press",

number = "5",

}

McMillin, 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, Giovannucci Uzielli, ML, 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 2014, 'Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker Syndrome, and distal arthrogryposis type 5', American Journal of Human Genetics, vol. 94, no. 5, pp. 734-744. https://doi.org/10.1016/j.ajhg.2014.03.015

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 - Giovannucci Uzielli, Maria Luisa

AU - Graham, John M.

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 - Bamshad, Michael J.

N1 - 1R01HD048895, NICHD NIH HHS, United States1RC2HG005608, NHGRI NIH HHS, United States1U54HG006493, NHGRI NIH HHS, United States5K23HD057331, NICHD NIH HHS, United States5R000HG004316, NHGRI NIH HHS, United States

PY - 2014/5/1

Y1 - 2014/5/1

N2 - 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. © 2014 The American Society of Human Genetics.

AB - 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. © 2014 The American Society of Human Genetics.

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 -

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

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