Identification of a prevalent founder mutation in an Israeli Muslim Arab village confirms the role of PRCD in the aetiology of retinitis pigmentosa in humans
Identification of a prevalent founder mutation in an Israeli Muslim Arab village confirms the role of PRCD in the aetiology of retinitis pigmentosa in humans
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DOI：
10.1136/jmg.2009.073619
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发表时间：
2010-08-01
影响因子：
4
通讯作者：
Ben-Yosef, T.
中科院分区：
文献类型：
--
作者：
Nevet, M. J.;Shalev, S. A.;Ben-Yosef, T.
背景：视网膜色素变性是遗传性视网膜变性最常见的表现形式。至少有32个基因和位点与非综合征常染色体隐性遗传性RP有关。进行性视杆-视锥变性是一种常染色体隐性遗传性视网膜变性的犬型，是人类RP的动物模型，由PrCD基因的错义突变引起。此前在孟加拉国的一例人类RP患者中也发现了相同的纯合子PrCD突变。方法对以色列北部一个与世隔绝的阿拉伯穆斯林村落进行单倍型分析，探讨常染色体隐性遗传性早幼粒细胞白血病高发病率的原因。通过对致病基因的直接测序来检测潜在的突变，并确定其在该村受影响和未受影响的个人中的流行率。对该突变纯合子的患者进行了眼底检查和视网膜电图检查。结果与结论报道了一种新的致病性PRCD无义突变。在9个家系的18例患者中发现了该创始人突变，其携带率在调查村为10%。该突变与典型的RP表型有关，包括骨针状色素沉积和不可记录的视网膜电信号。其他发现包括黄斑变性和白内障的迹象。在多个RP患者中发现了PrCD的第二个致病突变，证实了PrCD在人类RP病因学中的作用。
Background Retinitis pigmentosa (RP) is the most common form of hereditary retinal degeneration. At least 32 genes and loci have been implicated in non-syndromic autosomal recessive RP. Progressive rod-cone degeneration is a canine form of autosomal recessive retinal degeneration, which serves as an animal model for human RP, and is caused by a missense mutation of the PRCD gene. The same homozygous PRCD mutation has been previously identified in a single human RP patient from Bangladesh. To date, this is the only RP-causing mutation of PRCD reported in humans.Methods The cause of the high incidence rate of autosomal recessive RP in an isolated Muslim Arab village in Northern Israel was investigated by haplotype analysis in affected families. The underlying mutation was detected by direct sequencing of the causative gene, and its prevalence in affected and unaffected individuals from the village was determined. Patients who were homozygotes for this mutation underwent ophthalmic evaluation, including funduscopy and electroretinography.Results and conclusions The identification of a novel pathogenic nonsense mutation of PRCD is reported. This founder mutation was found in a homozygous state in 18 patients from nine families, and its carrier frequency in the investigated village is 10%. The mutation is associated with a typical RP phenotype, including bone spicule-type pigment deposits and non-recordable electroretinograms. Additional findings include signs of macular degeneration and cataract. The identification of a second pathogenic mutation of PRCD in multiple RP patients confirms the role of PRCD in the aetiology of RP in humans.