CEP290（NPHP6）基因的突变是莱伯先天性黑蒙的常见病因。
Mutations in the CEP290 (NPHP6) gene are a frequent cause of Leber congenital amaurosis.
作者信息
den Hollander Anneke I, Koenekoop Robert K, Yzer Suzanne, Lopez Irma, Arends Maarten L, Voesenek Krysta E J, Zonneveld Marijke N, Strom Tim M, Meitinger Thomas, Brunner Han G, Hoyng Carel B, van den Born L Ingeborgh, Rohrschneider Klaus, Cremers Frans P M
机构信息
Department of Human Genetics, Radboud University Nijmegen Medical Centre, 6500 HB Nijmegen, The Netherlands.
出版信息
Am J Hum Genet. 2006 Sep;79(3):556-61. doi: 10.1086/507318. Epub 2006 Jul 11.
Abstract
Leber congenital amaurosis (LCA) is one of the main causes of childhood blindness. To date, mutations in eight genes have been described, which together account for approximately 45% of LCA cases. We localized the genetic defect in a consanguineous LCA-affected family from Quebec and identified a splice defect in a gene encoding a centrosomal protein (CEP290). The defect is caused by an intronic mutation (c.2991+1655A-->G) that creates a strong splice-donor site and inserts a cryptic exon in the CEP290 messenger RNA. This mutation was detected in 16 (21%) of 76 unrelated patients with LCA, either homozygously or in combination with a second deleterious mutation on the other allele. CEP290 mutations therefore represent one of the most frequent causes of LCA identified so far.
摘要
莱伯先天性黑蒙（LCA）是儿童失明的主要原因之一。迄今为止，已发现八个基因发生突变，这些突变共同导致了约45%的LCA病例。我们对来自魁北克的一个患LCA的近亲家庭进行了基因缺陷定位，发现了一个编码中心体蛋白（CEP290）的基因存在剪接缺陷。该缺陷由一个内含子突变（c.2991+1655A→G）引起，该突变产生了一个强剪接供体位点，并在CEP290信使核糖核酸中插入了一个隐蔽外显子。在76例无关的LCA患者中，有16例（21%）检测到了这种突变，这些患者要么是纯合子，要么是另一个等位基因上存在第二个有害突变。因此，CEP290突变是迄今为止确定的LCA最常见的病因之一。
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