Novel and recurrent EVC and EVC2 mutations in Ellis-van Creveld syndrome and Weyers acrofacial dyostosis
Novel and recurrent EVC and EVC2 mutations in Ellis-van Creveld syndrome and Weyers acrofacial dyostosis
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DOI：
10.1016/j.ejmg.2012.11.005
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发表时间：
2013-02-01
影响因子：
1.9
通讯作者：
De Luca, Alessandro
中科院分区：
文献类型：
--
作者：
D'Asdia, Maria Cecilia;Torrente, Isabella;De Luca, Alessandro
埃利斯 - 范克里夫尔德综合征（Ellis van Creveld syndrome）和维厄斯面骨发育不全（Weyers acrofacial dysostosis）是由EVC或EVC2基因突变引起的等位基因疾病。我们展示了对32个临床诊断为埃利斯 - 范克里夫尔德综合征的无亲缘关系家庭以及2个维厄斯面骨发育不全家庭的整个EVC和EVC2基因编码区直接分析的结果。在32例埃利斯 - 范克里夫尔德综合征病例中，我们确定了27例（84%）存在突变，在2例维厄斯面骨发育不全病例中，2例均存在突变。在埃利斯 - 范克里夫尔德综合征病例中，27例中有20例（74%）在EVC基因存在突变，7例（26%）在EVC2基因存在突变。2例维厄斯面骨发育不全患者在EVC2的最后一个外显子存在杂合突变。我们总共检测到25个独立的EVC突变和11个独立的EVC2突变。19个EVC突变（19/25，76%）和4个EVC2突变（4/11，36%）是新的。在维厄斯面骨发育不全中发现的一个EVC2基因突变也是新的。在5例临床诊断为埃利斯 - 范克里夫尔德综合征的无亲缘关系病例中，我们在EVC和EVC2基因中均未发现任何突变。目前的研究结果扩展了埃利斯 - 范克里夫尔德综合征和维厄斯面骨发育不全的突变谱，并进一步证明EVC2基因的最后一个外显子是维厄斯面骨发育不全突变的热点。因此，对于疑似维厄斯面骨发育不全诊断的个体，在突变筛查中应优先分析EVC2外显子22。（C）2012爱思唯尔马松公司。版权所有。
Ellis van Creveld syndrome and Weyers acrofacial dysostosis are allelic disorders caused by mutations in EVC or EVC2 genes. We illustrate the results of direct analysis of whole EVC and EVC2 genes' coding regions in 32 unrelated families with clinical diagnosis of Ellis van Creveld syndrome and in 2 families with Weyers acrofacial dysostosis. We identified mutations in 27/32 (84%) cases with Ellis van Creveld syndrome and 2/2 cases with Weyers acrofacial dysostosis. Of the Ellis van Creveld syndrome cases, 20/27 (74%) had a mutation in EVC and 7/27 (26%) in EVC2 genes. The two subjects with Weyers acrofacial dysostosis had a heterozygous mutation in the last exon of EVC2. In total, we detected 25 independent EVC and 11 independent EVC2 mutations. Nineteen EVC mutations (19/25, 76%) and 4 EVC2 mutations (4/11, 36%) were novel. Also one EVC2 gene mutation found in Weyers acrofacial dysostosis was novel. In 5 unrelated cases with a clinical diagnosis of Ellis van Creveld syndrome, we did not find any mutation in either EVC or EVC2 genes. Current findings expand the Ellis van Creveld syndrome and Weyers acrofacial dysostosis mutation spectra, and provide further evidence that the last exon of EVC2 gene is a hot spot for Weyers acrofacial dysostosis mutations. Accordingly, EVC2 exon 22 should be analyzed with priority by mutation screening in individuals with a suspected diagnosis of Weyers acrofacial dysostosis. (C) 2012 Elsevier Masson SAS. All rights reserved.