Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients
Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients
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DOI：
10.1007/s00439-006-0237-7
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发表时间：
2007-01-01
期刊：
影响因子：
5.3
通讯作者：
Goodship, Judith A.
中科院分区：
文献类型：
--
作者：
Tompson, Stuart W. J.;Ruiz-Perez, Victor L.;Goodship, Judith A.
Ellis-van Creveld综合征（EvC）是由EvC和EVC2基因突变引起的，这两个基因在不同的方向上仅相隔2.6 kb。我们系统地在65个受影响个体中寻找这两个基因的突变，以评估由每个基因突变引起的病例比例。我们对这两个基因的编码外显子进行了PCR扩增和测序。我们通过体外剪接实验和cDNA分析来研究可能影响剪接的突变。我们在20例（31%）病例中发现EVC突变；在所有这些基因中，我们都检测到了每个等位基因上的突变。我们在25例（38%）病例中发现EVC2突变；在其中的22个中，我们在每个等位基因上分离出一个突变。大多数突变引入了一个过早终止密码子。我们对20例中没有发现任何基因突变的10例中两个基因之间的区域进行了测序，只发现了一个非常见多态性的SNP。由于我们在20例（31%）病例中未发现任何基因突变，因此可能存在进一步的遗传异质性。
Ellis-van Creveld syndrome (EvC) is caused by mutations in EVC and EVC2, genes in a divergent orientation separated by only 2.6 kb. We systematically sought mutations in both genes in a panel of 65 affected individuals to assess the proportion of cases resulting from mutations in each gene. We PCR amplified and sequenced the coding exons of both genes. We investigated mutations that could affect splicing by in vitro splicing assays and cDNA analysis. We have identified EVC mutations in 20 cases (31%); in all of these we have detected the mutation on each allele. We have identified EVC2 mutations in 25 cases (38%); in 22 of these we have isolated a mutation on each allele. The majority of the mutations introduce a premature termination codon. We sequenced the region between the two genes in 10 of the 20 cases in which we had not identified a mutation in either gene, revealing only one SNP that was not a common polymorphism. As we have not identified mutations in either gene in 20 cases (31%) it is possible that there is further genetic heterogeneity.