Deletions in the VPS13B(COH1) Gene as a Cause of Cohen Syndrome
Deletions in the VPS13B(COH1) Gene as a Cause of Cohen Syndrome
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DOI：
10.1002/humu.21065
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发表时间：
2009-09-01
期刊：
影响因子：
3.9
通讯作者：
Vermeesch, J. R.
中科院分区：
文献类型：
--
作者：
Balikova, I.;Lehesjoki, A-E.;Vermeesch, J. R.
科恩综合征是一种常染色体隐性遗传疾病，其特征在于智力迟钝、面部畸形、小头畸形、视网膜营养不良、躯干肥胖、关节松弛和间歇性中性粒细胞减少。VPS 13 B（COH 1）基因突变是科恩综合征的基础。在大约70%的患者中，在两个等位基因上鉴定出基因突变，而在大约30%的患者中，仅检测到单个等位基因中的突变或未检测到突变等位基因。VPS 13 B基因座最近被添加到良性拷贝数变异的不断增长的列表中。我们假设不明原因的科恩综合征患者可能存在影响VPS 13 B基因座的缺失。我们用靶向阵列CGH筛选了来自26个家族的35名患者，并鉴定了7个拷贝数改变：2个纯合缺失和5个杂合缺失。我们的研究结果表明，缺失是科恩综合征的一个重要原因，VPS 13 B拷贝数改变的筛查应该是这些患者诊断工作的一个组成部分。这些发现对于一般遗传性疾病患者的诊断具有重要意义，因为正如我们强调的，罕见的良性拷贝数变异可能是常染色体隐性遗传疾病的基础，并导致纯合状态或与另一种突变复合杂合性的疾病。(C)2009 Wiley-Liss，Inc.
Cohen syndrome is an autosomal recessive disorder that is characterized by mental retardation, facial dysmorphism, microcephaly, retinal dystrophy, truncal obesity, joint laxity and intermittent neutropenia. Mutations in the VPS13B (COH1) gene underlie Cohen syndrome. In approximately 70% of the patients mutations in the gene are identified on both alleles, while in about 30% only a mutation in a single allele or no mutant allele is detected. The VPS13B locus was recently added to the growing list of benign copy number variants. We hypothesized that patients with unexplained Cohen syndrome would harbour deletions affecting the VPS13B locus. We screened 35 patients from 26 families with targeted array CGH and identified 7 copy number alterations: 2 homozygous and 5 heterozygous deletions. Our results show that deletions are an important cause of Cohen syndrome and screening for copy number alterations of VPS13B should be an integral part of the diagnostic work-up of these patients. These findings have important consequences for the diagnosis of patients with genetic disorders in general since, as we highlight, rare benign copy number variants can underly autosomal recessive disorders and lead to disease in homozygous state or in compound heterozygosity with another mutation. (C) 2009 Wiley-Liss, Inc.