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In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome

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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 inframe 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-beta 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-beta-signaling pathway.
Keywords
CRANIOSYNOSTOSIS, REPRESSION, PROTOONCOGENE, MICE, DACHSHUND

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Chicago
Carmignac, Virgini, Julien Thevenon, Lesly Adès, Bert Callewaert, Sophie Julia, Christel Thauvin-Robinet, Lucie Gueneau, et al. 2012. “In-frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome.” American Journal of Human Genetics 91 (5): 950–957.
APA
Carmignac, V., Thevenon, J., Adès, L., Callewaert, B., Julia, S., Thauvin-Robinet, C., Gueneau, L., et al. (2012). In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome. AMERICAN JOURNAL OF HUMAN GENETICS, 91(5), 950–957.
Vancouver
1.
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;91(5):950–7.
MLA
Carmignac, Virgini, Julien Thevenon, Lesly Adès, et al. “In-frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome.” AMERICAN JOURNAL OF HUMAN GENETICS 91.5 (2012): 950–957. Print.
@article{3101685,
  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 inframe 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-beta 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-beta-signaling pathway.},
  author       = {Carmignac, Virgini and Thevenon, Julien and Ad{\`e}s, Lesly and Callewaert, Bert and Julia, Sophie and Thauvin-Robinet, Christel and Gueneau, Lucie and Courcet, Jean-Benoit and Lopez, Estelle and Holman, Katherine and Renard, Marjolijn and Plauchu, Henri and Plessis, Ghislaine and De Backer, Julie and Child, Anne and Arno, Gavin and Duplomb, Laurence and Callier, Patrick and Aral, Beranrd and Vabres, Pierre and Gigot, Nad{\`e}ge and Arbustini, Eloisa and Grasso, Maurizia and Robinson, Peter and Goizet, Cyril and Baumann, Clarisse and Di Rocco, Maja and Sanchez Del Pozo, Jaime and Huet, Fr{\'e}d{\'e}ric and Jondeau, Guillaume and Collod-Beroud, Gwena{\"e}lle and Beroud, Christophe and Amiel, Jeanne and Cormier-Daire, Val{\'e}rie and Rivi{\`e}re, Jean-Baptiste and Boileau, Catherine and De Paepe, Anne and Faivre, Laurence},
  issn         = {0002-9297},
  journal      = {AMERICAN JOURNAL OF HUMAN GENETICS},
  keyword      = {CRANIOSYNOSTOSIS,REPRESSION,PROTOONCOGENE,MICE,DACHSHUND},
  language     = {eng},
  number       = {5},
  pages        = {950--957},
  title        = {In-frame mutations in exon 1 of SKI cause dominant Shprintzen-Goldberg syndrome},
  url          = {http://dx.doi.org/10.1016/j.ajhg.2012.10.002},
  volume       = {91},
  year         = {2012},
}

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