A Common Mutation in the CBS Gene Explains a High Incidence of Homocystinuria in the Qatari Population
A Common Mutation in the CBS Gene Explains a High Incidence of Homocystinuria in the Qatari Population
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DOI：
10.1002/humu.9436
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发表时间：
2006-07-01
期刊：
影响因子：
3.9
通讯作者：
Zschocke, Johannes
中科院分区：
文献类型：
--
作者：
El-Said, Mahmoud F.;Badii, Ramin;Zschocke, Johannes
我们报告的结果进行了研究，以描绘在卡塔尔人口的同型胱氨酸尿症的遗传和流行病学方面。64例同型胱氨酸尿症患者（男37例，女27例，年龄1 ~ 29岁）来自31个核心家庭，在一段时间内超过四年的确定。据计算，卡塔尔的同型胱氨酸尿症发病率为>= 1：3000，是迄今为止世界上已知的最高发病率。所有数据可用的患者均为维生素B-6无反应。对所有患者进行了分子生物学研究。来自M部落的所有53名患者和来自K部落的所有3名患者都是CBS基因突变c.1006C>T（p.R336C）的纯合子，另外7名患者来自M部落和K部落之间的混合婚姻。来自S部落的单个患者是CBS基因中突变c.700G>A（p.D234N）的纯合型。这两种突变以前都有报道，但涉及高变CpG dinculeotides，可能是卡塔尔人群中的复发突变。这项研究的结果说明了一个强大的创始人效应，导致高患病率的常染色体隐性遗传病在一个高度血亲阿拉伯人口。新生儿分子筛查可能适用于早期发现同型胱氨酸尿症在这一人群中。(C)2006 Wiley-Liss，Inc.
We report the results of a study carried out to delineate genetic and epidemiological aspects of homocystinuria in the Qatari population. Sixty-four patients with homocystinuria (37 males, 27 females, age 1 to 29 years) from 31 nuclear families were ascertained over a period of more than four years. The incidence of homocystinuria in Qatar was calculated to be >= 1:3000, the highest in the world known so far. All patients in whom data were available were vitamin B-6-nonresponsive. Molecular studies were performed in all patients. All 53 patients from tribe M and all three patients from tribe K were homozygous for the mutation c.1006C>T (p.R336C) in the CBS gene, with an additional seven patients resulting from mixed marriages between tribe M and tribe K. A single patient from tribe S was homozygous for mutation c.700G>A (p.D234N) in the CBS gene. Both mutations have been previously reported but involve hypermutable CpG dinculeotides and may be recurrent mutations in the Qatari population. The results of this study illustrate a strong founder effect causing a high prevalence of an autosomal recessive disease in a highly consanguineous Arabian population. Molecular neonatal screening may be suitable for early detection of homocystinuria in this population. (C) 2006 Wiley-Liss, Inc.