巴德-比德尔综合征患者的外显子组测序鉴定出BBSome亚基BBIP1（BBS18）中的一个无效突变。
Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18).
作者信息
Scheidecker Sophie, Etard Christelle, Pierce Nathan W, Geoffroy Véronique, Schaefer Elise, Muller Jean, Chennen Kirsley, Flori Elisabeth, Pelletier Valérie, Poch Olivier, Marion Vincent, Stoetzel Corinne, Strähle Uwe, Nachury Maxence V, Dollfus Hélène
机构信息
Laboratoire de Génétique Médicale, INSERM U1112, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.
出版信息
J Med Genet. 2014 Feb;51(2):132-6. doi: 10.1136/jmedgenet-2013-101785. Epub 2013 Sep 11.
Abstract
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.
摘要
背景
巴德-比埃尔综合征（BBS）是一种隐性且基因异质性的纤毛病，其特征为色素性视网膜炎、肥胖、肾功能不全、轴后多指畸形、行为功能障碍和性腺功能减退。迄今为止鉴定出的17种BBS基因产物中的7种与蛋白质BBIP1/BBIP10一起组装成BBSome，这是一种蛋白质复合物，可将信号受体运入和运出纤毛。
方法与结果
对一例散发的BBS病例进行外显子组测序，首次在BBIP1基因中发现了一个纯合的终止突变（NM_001195306: c.173T>G, p.Leu58*）。该突变具有致病性，因为在患者的成纤维细胞中未检测到BBIP1蛋白，且BBIP1[Leu58*]无法与BBSome亚基BBS4结合。
结论
这些发现将BBIP1确定为第18个BBS基因（BBS18），并表明BBSome组装可能代表BBS的一种统一发病机制。
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