Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis
Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis
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DOI：
10.1038/73508
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发表时间：
2000-03-01
期刊：
影响因子：
30.8
通讯作者：
Goodship, J
中科院分区：
文献类型：
--
作者：
Ruiz-Perez, VL;Ide, SE;Goodship, J
Ellis-van Creveld综合征（EvC，MIM 225500）是一种常染色体隐性遗传性骨骼发育不良，其特征为短肢、短肋骨、轴后多指（趾）畸形以及指甲和牙齿发育不良（1，2）。先天性心脏缺陷，最常见的是原发性房间隔缺陷产生一个共同的心房，发生在60%的受影响的个人。在来自墨西哥、厄瓜多尔和巴西的9个阿米什亚谱系和单谱系中，该疾病被定位于染色体4p 16（3）。Weyers肢端骨发育不全（MIM 193530）是一种常染色体显性遗传疾病，具有相似但更温和的表型，已在一个家系中定位到包括EvC关键区域的区域（4）。我们已经确定了一个新的基因（EVC），编码一个992个氨基酸的蛋白质，这是突变的个人与EvC。我们确定了一个剪接供体的变化，在阿米什人家系和6个截断突变和一个单一的氨基酸缺失在7个家系。这些突变的杂合子携带者没有表现出EvC的特征。我们发现了两个与表型相关的杂合错义突变，一个发生在Weyers肢端骨发育不全的男性中，另一个发生在父亲和他的女儿中，他们都有EvC和多指（趾）畸形的心脏缺陷特征，但不是身材矮小。我们认为，EvC和Weyers肢端骨发育不全是等位基因：条件。
Ellis-van Creveld syndrome (EvC, MIM 225500) is an autosomal recessive skeletal dysplasia characterized by short limbs, short ribs, postaxial polydactyly and dysplastic nails and teeth(1,2). Congenital cardiac defects, most commonly a defect of primary atrial septation producing a common atrium, occur in 60% of affected individuals. The disease was mapped to chromosome 4p16 in nine Amish subpedigrees and single pedigrees from Mexico, Ecuador and Brazil(3). Weyers acrodental dysostosis (MIM 193530), an autosomal dominant disorder with a similar but milder phenotype, has been mapped in a single pedigree to an area including the EvC critical region(4). We have identified a new gene (EVC), encoding a 992-amino-acid protein, that is mutated in individuals with EvC. We identified a splice-donor change in an Amish pedigree and six truncating mutations and a single amino acid deletion in seven pedigrees. The heterozygous carriers of these mutations did not manifest features of EvC. We found two heterozygous missense mutations associated with a phenotype, one in a man with Weyers acrodental dysostosis and another in a father and his daughter, who both have the heart defect characteristic of EvC and polydactyly, but not short stature. We suggest that EvC and Weyers acrodental dysostosis are allelic: conditions.