In-Frame Mutations in Exon 1 of SKI Cause Dominant Shprintzen-Goldberg Syndrome

被引：73

作者：

Carmignac, Virginie ^{[1
]}

Thevenon, Julien ^{[1
,2
,3
]}

Ades, Lesley ^{[4
,5
,6
]}

Callewaert, Bert ^{[7
]}

Julia, Sophie ^{[8
]}

Thauvin-Robinet, Christel ^{[1
,2
,3
]}

Gueneau, Lucie ^{[1
]}

Courcet, Jean-Benoit ^{[1
]}

Lopez, Estelle ^{[1
]}

Holman, Katherine ^{[4
,5
,6
]}

Renard, Marjolijn ^{[7
]}

Plauchu, Henri ^{[9
,10
]}

Plessis, Ghislaine ^{[11
]}

De Backer, Julie ^{[7
]}

Child, Anne ^{[12
]}

Arno, Gavin ^{[12
]}

Duplomb, Laurence ^{[1
]}

Callier, Patrick ^{[1
,13
]}

Aral, Bernard ^{[1
,14
]}

Vabres, Pierre ^{[1
,15
]}

Gigot, Nadege ^{[1
]}

Arbustini, Eloisa ^{[16
]}

Grasso, Maurizia ^{[16
]}

Robinson, Peter N. ^{[17
]}

Goizet, Cyril ^{[18
,19
]}

Baumann, Clarisse ^{[20
]}

Di Rocco, Maja ^{[21
]}

Sanchez Del Pozo, Jaime ^{[22
]}

Huet, Frederic ^{[1
]}

Jondeau, Guillaume ^{[23
,24
]}

Collod-Beroud, Gwenaelle ^{[25
]}

Beroud, Christophe ^{[25
,26
]}

Amiel, Jeanne ^{[26
]}

Cormier-Daire, Valerie ^{[27
,28
]}

Riviere, Jean-Baptiste ^{[1
]}

Boileau, Catherine ^{[29
]}

De Paepe, Anne ^{[7
]}

Faivre, Laurence ^{[1
,2
,3
]}

机构：

[1] Univ Bourgogne, Equipe Genet Anomalies Dev, Equipe Accueil 4271, F-21079 Dijon, France

[2] Hop Enfants, Ctr Genet, F-21079 Dijon, France

[3] Hop Enfants, Ctr Reference Anomalies Dev & Syndromes Malformat, F-21079 Dijon, France

[4] Childrens Hosp Westmead, Marfan Res Grp, Sydney, NSW 2006, Australia

[5] Univ Sydney, Discipline Paediat & Child Hlth, Sydney, NSW 2006, Australia

[6] Childrens Hosp Westmead, Dept Clin Genet, Sydney, NSW 2006, Australia

[7] Ghent Univ Hosp, Ctr Med Genet, B-9000 Ghent, Belgium

[8] CHU Purpan, Serv Genet, F-31000 Toulouse, France

[9] Univ Lyon 1, Dept Genet, F-69977 Bron, France

[10] Hosp Civils Lyon, Hop Louis Pradel, F-69977 Bron, France

[11] CHU Caen, Serv Genet, F-14033 Caen 9, France

[12] St Georges Univ London, Dept Cardiac & Vasc Sci, London SW17 0RE, England

[13] Ctr Hosp Univ, Cytogenet Serv, F-21079 Dijon, France

[14] Ctr Hosp Univ, Serv Biol Mol, F-21079 Dijon, France

[15] Ctr Hosp Univ Bocage, Serv Dermatol, F-21079 Dijon, France

[16] Policlin San Matteo, Fdn Ist Ricovero & Cura Carattere Sci, Ctr Inherited Cardiovasc Dis, I-27100 Pavia, Italy

[17] Charite, Inst Med Genet & Humangenet, D-13353 Berlin, Germany

[18] Ctr Hosp Univ Bordeaux, Hop Pellegrin, Serv Genet, Ctr Reference Anomalies Dev, F-33076 Bordeaux, France

[19] Univ Bordeaux, Lab Malad Rares Genet & Metab, Equipe Accueil 4576, F-33076 Bordeaux, France

[20] Hop Robert Debre, AP HP, Serv Genet Med, F-75019 Paris, France

[21] Gaslini Inst, Dept Pediat, Unit Rare Dis, I-16147 Genoa, Italy

[22] Hosp 12 Octubre, Div Endocrinol, Dept Genet, Madrid 28041, Spain

[23] INSERM, U698, F-75877 Paris, France

[24] Hop Bichat Claude Bernard, AP HP, Ctr Reference Syndromes Marfan & Apparentes, F-75877 Paris, France

[25] Univ Aix Marseille, INSERM, UMR S 910, F-13100 Marseille, France

[26] Hop Enfants La Timone, Assistance Publ Hop Marseille, Dept Med Genet, F-13000 Marseille, France

[27] Univ Paris Descartes Sorbonne Paris Cite, Hop Necker Enfants Malad, AP HP, INSERM,Fdn Imagine,U781, F-75015 Paris, France

[28] Univ Paris Descartes Sorbonne Paris Cite, Hop Necker Enfants Malad, AP HP, Fdn Imagine,Dept Genet, F-75015 Paris, France

[29] Univ Versailles St Quentin Yvelines, Hop Ambroise Pare, AP HP, Lab Genet Mol, F-92104 Boulogne, France

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2012年 / 91卷 / 05期

关键词：

CRANIOSYNOSTOSIS; PROTOONCOGENE; REPRESSION; DACHSHUND; MICE;

D O I：

10.1016/j.ajhg.2012.10.002

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：950 / 957

页数：8

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