Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18)

被引：101

作者：

Scheidecker, Sophie ^{[1
]}

Etard, Christelle ^{[2
]}

Pierce, Nathan W. ^{[3
]}

Geoffroy, Veronique ^{[4
]}

Schaefer, Elise ^{[1
,5
]}

Muller, Jean ^{[6
,7
]}

Chennen, Kirsley ^{[1
,7
]}

Flori, Elisabeth ^{[8
]}

Pelletier, Valerie ^{[5
]}

Poch, Olivier ^{[7
]}

Marion, Vincent ^{[1
]}

Stoetzel, Corinne ^{[1
]}

Straehle, Uwe ^{[2
]}

Nachury, Maxence V. ^{[3
]}

Dollfus, Helene ^{[1
,5
]}

机构：

[1] Univ Strasbourg, INSERM, U1112, Lab Genet Med,FMTS, F-67085 Strasbourg, France

[2] Karlsruher Inst Technol, Inst Toxikol & Genet Campus Nord, Eggenstein Leopoldshafen, Germany

[3] Stanford Univ, Sch Med, Dept Mol & Cellular Physiol, Stanford, CA 94305 USA

[4] Univ Strasbourg, Plate Forme Bioinformat Strasbourg, IGBMC, CNRS,UMR7104,INSERM,U964, Illkirch Graffenstaden, France

[5] Hop Univ Strasbourg, Ctr Reference Affect Rares Genet Ophtalmol CARGO, Gen Med Serv, Strasbourg, France

[6] Hop Univ Strasbourg, Lab Diagnost Genet, Strasbourg, France

[7] Univ Strasbourg, Integrat Genom & Bioinformat Lab, IGBMC, CNRS,UMR7104,INSERM,U964,ICube,UMR 7357, Illkirch Graffenstaden, France

[8] Hop Univ Strasbourg, Cytogenet Serv, Strasbourg, France

来源：

JOURNAL OF MEDICAL GENETICS | 2014年 / 51卷 / 02期

关键词：

Clinical Genetics; Diagnostics Tests; Genetic Screening; Counselling; Molecular Genetics; Ophthalmology; DIAGNOSIS; PROTEINS; COMPLEX;

D O I：

10.1136/jmedgenet-2013-101785

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background Bardet-Biedl syndrome (BBS) is a recessive and genetically heterogeneous ciliopathy characterised by retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioural dysfunction and hypogonadism. 7 of the 17 BBS gene products identified to date assemble together with the protein BBIP1/BBIP10 into the BBSome, a protein complex that ferries signalling receptors to and from cilia. Methods and results Exome sequencing performed on a sporadic BBS case revealed for the first time a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. This mutation is pathogenic since no BBIP1 protein could be detected in fibroblasts from the patient, and BBIP1[Leu58*] is unable to associate with the BBSome subunit BBS4. Conclusions These findings identify BBIP1 as the 18th BBS gene (BBS18) and suggest that BBSome assembly may represent a unifying pathomechanism for BBS.

引用

页码：132 / 136

页数：5

共 19 条

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