In search of triallelism in Bardet-Biedl syndrome
In search of triallelism in Bardet-Biedl syndrome
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DOI：
10.1038/ejhg.2011.205
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发表时间：
2012-04-01
影响因子：
5.2
通讯作者：
Alkuraya, Fowzan S.
中科院分区：
文献类型：
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作者：
Abu-Safieh, Leen;Al-Anazi, Shamsa;Alkuraya, Fowzan S.
Bardet-Biedl综合征（BBS）是人类纤毛病变的模型疾病。显著的遗传异质性，这种疾病的特点是一致的积累数据之间的相互作用的蛋白质编码的14个BBS基因的日期。之前的报告表明，这种相互作用也可能扩展到三等位基因形式的寡基因遗传的情况，这违背了长期以来将BBS视为常染色体隐性疾病的观点。为了研究BBS中三等位性的大小，我们对29个BBS家族的所有14个BBS基因以及CCDC 28 B修饰基因进行了综合分析，其中大多数是多重的。在这些家族中的每个家族中鉴定出BBS基因中的两个反式突变，总共20个突变，包括12个新突变。在任何情况下，我们都没有观察到两个突变，在一个给定的家庭未受影响的成员，或观察到的第三个等位基因的存在，令人信服地作为一个修改器的突变率，并支持三等位基因模型的BBS。除了提出一个全面的基因型/表型概述了一个大的BBS突变，包括非综合征性视网膜色素变性的发生在一个家庭与一个新的BBS 9突变，我们的研究认为，在大多数情况下，赞成直接的常染色体隐性BBS。European Journal of Human Genetics（2012）20，420-427; doi：10.1038/ejhg.2011.205; 2012年2月22日在线发表
Bardet-Biedl syndrome (BBS) is a model disease for ciliopathy in humans. The remarkable genetic heterogeneity that characterizes this disease is consistent with accumulating data on the interaction between the proteins encoded by the 14 BBS genes identified to date. Previous reports suggested that such interaction may also extend to instances of oligogenic inheritance in the form of triallelism which defies the long held view of BBS as an autosomal recessive disease. In order to investigate the magnitude of triallelism in BBS, we conducted a comprehensive analysis of all 14 BBS genes as well as the CCDC28B-modifier gene in a cohort of 29 BBS families, most of which are multiplex. Two in trans mutations in a BBS gene were identified in each of these families for a total of 20 mutations including 12 that are novel. In no instance did we observe two mutations in unaffected members of a given family, or observe the presence of a third allele that convincingly acted as a modifier of penetrance and supported the triallelic model of BBS. In addition to presenting a comprehensive genotype/phenotype overview of a large set of BBS mutations, including the occurrence of nonsyndromic retinitis pigmentosa in a family with a novel BBS9 mutation, our study argues in favor of straightforward autosomal recessive BBS in most cases. European Journal of Human Genetics (2012) 20, 420-427; doi: 10.1038/ejhg.2011.205; published online 22 February 2012