• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Canadian journal of ophthalmology >Leber's congenital amaurosis with anterior keratoconus in Pakistani families is caused by the Trp278X mutation in the AIPL1 gene on 17p.
【24h】

Leber's congenital amaurosis with anterior keratoconus in Pakistani families is caused by the Trp278X mutation in the AIPL1 gene on 17p.

机译：巴基斯坦家庭的Leber先天性黑锥病与圆锥角膜前突是由AIPL1基因在17p处的Trp278X突变引起的。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

BACKGROUND: Leber's congenital amaurosis (LCA) represents the earliest and severest form of retinal dystrophy leading to congenital blindness. A total of 20% of children attending blind schools have this disease. LCA has a multigenic basis and is proving central to our understanding of the development of the retina. We describe the clinical and molecular genetic features of four inbred pedigrees from neighbouring remote villages in northern Pakistan, in which some of the affected members have concurrent keratoconus. METHODS: History-taking and physical and eye examinations were performed in the field. Venipuncture, DNA extraction, studies of linkage to known LCA genes, automated sequencing and polymorphism analyses for haplotype assessments were done. RESULTS: We examined 12 affected and 15 unaffected family members. By history, there were an additional nine blind people in the four pedigrees. In each pedigree a consanguineous marriage was evident. We found a homozygous nonsense mutation in the AIPL1 gene, which replaces a tryptophan with a stop codon (Trp278X). The phenotype is severe and variable, despite the common molecular genetic etiology in each family. Affected patients had hand motion to no light perception vision and fundus findings ranging from maculopathy to diffuse pigmentary retinopathy. Three affected members had definite keratoconus, and two were suspects based on mild cone formation in the cornea of at least one eye. INTERPRETATION: We have identified four Pakistani families with a severe form of LCA that is associated with severe keratoconus in some affected members. The molecular etiology in all four families is a homozygous nonsense mutation, Trp278X, in the photoreceptor-pineal gene AIPL1. To our knowledge, this is one of the first phenotype-genotype correlations of AIPL1-associated LCA.
机译：背景：莱伯（Leber）先天性黑蒙病（LCA）代表视网膜营养不良的最早和最严重形式，导致先天性失明。总共有20％的盲校儿童患有这种疾病。 LCA具有多基因基础，并且被证明对我们对视网膜发育的理解至关重要。我们描述了巴基斯坦北部邻近偏远村庄的四个近交家系的临床和分子遗传学特征，其中一些受影响的成员同时患有圆锥角膜。方法：在现场进行了历史记录以及身体和眼睛检查。进行了静脉穿刺，DNA提取，与已知LCA基因的连锁研究，用于单倍型评估的自动测序和多态性分析。结果：我们检查了12位受影响的家庭成员和15位未受影响的家庭成员。从历史上看，在四个血统书中还有九个盲人。在每个血统中，都是近亲通婚。我们在AIPL1基因中发现了纯合性无意义突变，该突变用终止密码子（Trp278X）取代了色氨酸。尽管每个家庭都有共同的分子遗传病因，但该表型是严重且可变的。受影响的患者有手部动作，无光感视力，眼底发现范围从黄斑病到弥漫性色素性视网膜病。三名受影响的成员患有确定的圆锥角膜，而两名怀疑是基于至少一只眼睛的角膜中出现轻度圆锥形成。口译：我们已经鉴定出四个巴基斯坦家庭，他们患有严重的LCA，在一些受影响的成员中与严重的圆锥角膜有关。所有这四个家族的分子病因学是光感受器-松果基因AIPL1中的纯合性无义突变Trp278X。据我们所知，这是与AIPL1相关的LCA的第一个表型-基因型相关性。

著录项

相似文献

  • 外文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号