In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome

Virginie Carmignac, Julien Thevenon, Lesley Adès, Bert Callewaert, Sophie Julia, Christel Thauvin-Robinet, Lucie Gueneau, Jean Benoit Courcet, Estelle Lopez, Katherine Holman, Marjolijn Renard, Henri Plauchu, Ghislaine Plessis, Julie De Backer, Anne Child, Gavin Arno, Laurence Duplomb, Patrick Callier, Bernard Aral, Pierre VabresNadège Gigot, Eloisa Arbustini, Maurizia Grasso, Peter N. Robinson, Cyril Goizet, Clarisse Baumann, Maja Di Rocco, Jaime Sanchez Del Pozo, Frédéric Huet, Guillaume Jondeau, Gwenaëlle Collod-Beroud, Christophe Beroud, Jeanne Amiel, Valérie Cormier-Daire, Jean Baptiste Rivière, Catherine Boileau, Anne De Paepe, Laurence Faivre

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mutation was found in a cohort of 11 individuals with other marfanoid-craniosynostosis phenotypes. The interaction between SKI and Smad2/3 and Smad 4 regulates TGF-β signaling, and the pattern of anomalies in Ski-deficient mice corresponds to the clinical manifestations of SGS. These findings define SGS as a member of the family of diseases associated with the TGF-β-signaling pathway.

Original languageEnglish
Pages (from-to)950-957
Number of pages8
JournalAmerican Journal of Human Genetics
Volume91
Issue number5
DOIs
Publication statusPublished - Nov 2 2012

Fingerprint

Exons
Craniosynostoses
Mutation
Exome
Mosaicism
Missense Mutation
Intellectual Disability
Phenotype
Shprintzen Golberg craniosynostosis

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Carmignac, V., Thevenon, J., Adès, L., Callewaert, B., Julia, S., Thauvin-Robinet, C., ... Faivre, L. (2012). In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome. American Journal of Human Genetics, 91(5), 950-957. https://doi.org/10.1016/j.ajhg.2012.10.002

In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome. / Carmignac, Virginie; Thevenon, Julien; Adès, Lesley; Callewaert, Bert; Julia, Sophie; Thauvin-Robinet, Christel; Gueneau, Lucie; Courcet, Jean Benoit; Lopez, Estelle; Holman, Katherine; Renard, Marjolijn; Plauchu, Henri; Plessis, Ghislaine; De Backer, Julie; Child, Anne; Arno, Gavin; Duplomb, Laurence; Callier, Patrick; Aral, Bernard; Vabres, Pierre; Gigot, Nadège; Arbustini, Eloisa; Grasso, Maurizia; Robinson, Peter N.; Goizet, Cyril; Baumann, Clarisse; Di Rocco, Maja; Sanchez Del Pozo, Jaime; Huet, Frédéric; Jondeau, Guillaume; Collod-Beroud, Gwenaëlle; Beroud, Christophe; Amiel, Jeanne; Cormier-Daire, Valérie; Rivière, Jean Baptiste; Boileau, Catherine; De Paepe, Anne; Faivre, Laurence.

In: American Journal of Human Genetics, Vol. 91, No. 5, 02.11.2012, p. 950-957.

Research output: Contribution to journalArticle

Carmignac, V, Thevenon, J, Adès, L, Callewaert, B, Julia, S, Thauvin-Robinet, C, Gueneau, L, Courcet, JB, Lopez, E, Holman, K, Renard, M, Plauchu, H, Plessis, G, De Backer, J, Child, A, Arno, G, Duplomb, L, Callier, P, Aral, B, Vabres, P, Gigot, N, Arbustini, E, Grasso, M, Robinson, PN, Goizet, C, Baumann, C, Di Rocco, M, Sanchez Del Pozo, J, Huet, F, Jondeau, G, Collod-Beroud, G, Beroud, C, Amiel, J, Cormier-Daire, V, Rivière, JB, Boileau, C, De Paepe, A & Faivre, L 2012, 'In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome', American Journal of Human Genetics, vol. 91, no. 5, pp. 950-957. https://doi.org/10.1016/j.ajhg.2012.10.002
Carmignac V, Thevenon J, Adès L, Callewaert B, Julia S, Thauvin-Robinet C et al. In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome. American Journal of Human Genetics. 2012 Nov 2;91(5):950-957. https://doi.org/10.1016/j.ajhg.2012.10.002
Carmignac, Virginie ; Thevenon, Julien ; Adès, Lesley ; Callewaert, Bert ; Julia, Sophie ; Thauvin-Robinet, Christel ; Gueneau, Lucie ; Courcet, Jean Benoit ; Lopez, Estelle ; Holman, Katherine ; Renard, Marjolijn ; Plauchu, Henri ; Plessis, Ghislaine ; De Backer, Julie ; Child, Anne ; Arno, Gavin ; Duplomb, Laurence ; Callier, Patrick ; Aral, Bernard ; Vabres, Pierre ; Gigot, Nadège ; Arbustini, Eloisa ; Grasso, Maurizia ; Robinson, Peter N. ; Goizet, Cyril ; Baumann, Clarisse ; Di Rocco, Maja ; Sanchez Del Pozo, Jaime ; Huet, Frédéric ; Jondeau, Guillaume ; Collod-Beroud, Gwenaëlle ; Beroud, Christophe ; Amiel, Jeanne ; Cormier-Daire, Valérie ; Rivière, Jean Baptiste ; Boileau, Catherine ; De Paepe, Anne ; Faivre, Laurence. / In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome. In: American Journal of Human Genetics. 2012 ; Vol. 91, No. 5. pp. 950-957.
@article{0a736caecb7a4e629710ee0350159db6,
title = "In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome",
abstract = "Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mutation was found in a cohort of 11 individuals with other marfanoid-craniosynostosis phenotypes. The interaction between SKI and Smad2/3 and Smad 4 regulates TGF-β signaling, and the pattern of anomalies in Ski-deficient mice corresponds to the clinical manifestations of SGS. These findings define SGS as a member of the family of diseases associated with the TGF-β-signaling pathway.",
author = "Virginie Carmignac and Julien Thevenon and Lesley Ad{\`e}s and Bert Callewaert and Sophie Julia and Christel Thauvin-Robinet and Lucie Gueneau and Courcet, {Jean Benoit} and Estelle Lopez and Katherine Holman and Marjolijn Renard and Henri Plauchu and Ghislaine Plessis and {De Backer}, Julie and Anne Child and Gavin Arno and Laurence Duplomb and Patrick Callier and Bernard Aral and Pierre Vabres and Nad{\`e}ge Gigot and Eloisa Arbustini and Maurizia Grasso and Robinson, {Peter N.} and Cyril Goizet and Clarisse Baumann and {Di Rocco}, Maja and {Sanchez Del Pozo}, Jaime and Fr{\'e}d{\'e}ric Huet and Guillaume Jondeau and Gwena{\"e}lle Collod-Beroud and Christophe Beroud and Jeanne Amiel and Val{\'e}rie Cormier-Daire and Rivi{\`e}re, {Jean Baptiste} and Catherine Boileau and {De Paepe}, Anne and Laurence Faivre",
year = "2012",
month = "11",
day = "2",
doi = "10.1016/j.ajhg.2012.10.002",
language = "English",
volume = "91",
pages = "950--957",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - In-frame mutations in exon 1 of SKI cause dominant shprintzen-goldberg syndrome

AU - Carmignac, Virginie

AU - Thevenon, Julien

AU - Adès, Lesley

AU - Callewaert, Bert

AU - Julia, Sophie

AU - Thauvin-Robinet, Christel

AU - Gueneau, Lucie

AU - Courcet, Jean Benoit

AU - Lopez, Estelle

AU - Holman, Katherine

AU - Renard, Marjolijn

AU - Plauchu, Henri

AU - Plessis, Ghislaine

AU - De Backer, Julie

AU - Child, Anne

AU - Arno, Gavin

AU - Duplomb, Laurence

AU - Callier, Patrick

AU - Aral, Bernard

AU - Vabres, Pierre

AU - Gigot, Nadège

AU - Arbustini, Eloisa

AU - Grasso, Maurizia

AU - Robinson, Peter N.

AU - Goizet, Cyril

AU - Baumann, Clarisse

AU - Di Rocco, Maja

AU - Sanchez Del Pozo, Jaime

AU - Huet, Frédéric

AU - Jondeau, Guillaume

AU - Collod-Beroud, Gwenaëlle

AU - Beroud, Christophe

AU - Amiel, Jeanne

AU - Cormier-Daire, Valérie

AU - Rivière, Jean Baptiste

AU - Boileau, Catherine

AU - De Paepe, Anne

AU - Faivre, Laurence

PY - 2012/11/2

Y1 - 2012/11/2

N2 - Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mutation was found in a cohort of 11 individuals with other marfanoid-craniosynostosis phenotypes. The interaction between SKI and Smad2/3 and Smad 4 regulates TGF-β signaling, and the pattern of anomalies in Ski-deficient mice corresponds to the clinical manifestations of SGS. These findings define SGS as a member of the family of diseases associated with the TGF-β-signaling pathway.

AB - Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI further identified one overlapping heterozygous in-frame deletion and ten heterozygous missense mutations affecting recurrent residues in 18 of the 19 individuals screened for SGS; these individuals included one family affected by somatic mosaicism. All mutations were located in a restricted area of exon 1, within the R-SMAD binding domain of SKI. No mutation was found in a cohort of 11 individuals with other marfanoid-craniosynostosis phenotypes. The interaction between SKI and Smad2/3 and Smad 4 regulates TGF-β signaling, and the pattern of anomalies in Ski-deficient mice corresponds to the clinical manifestations of SGS. These findings define SGS as a member of the family of diseases associated with the TGF-β-signaling pathway.

UR - http://www.scopus.com/inward/record.url?scp=84868498164&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868498164&partnerID=8YFLogxK

U2 - 10.1016/j.ajhg.2012.10.002

DO - 10.1016/j.ajhg.2012.10.002

M3 - Article

C2 - 23103230

AN - SCOPUS:84868498164

VL - 91

SP - 950

EP - 957

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 5

ER -