A Founder Large Deletion Mutation in Xeroderma Pigmentosum-Variant Form in Tunisia: Implication for Molecular Diagnosis and Therapy
A Founder Large Deletion Mutation in Xeroderma Pigmentosum-Variant Form in Tunisia: Implication for Molecular Diagnosis and Therapy
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DOI：
10.1155/2014/256245
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发表时间：
2014-01-01
影响因子：
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通讯作者：
Yacoub-Youssef, Houda
中科院分区：
文献类型：
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作者：
Ben Rekaya, Mariem;Laroussi, Nadia;Yacoub-Youssef, Houda
变异型着色性干皮病(XP-V)的特点是皮肤症状起病晚。我们的目标是对XP-V突尼斯患者进行临床和基因调查，以开发一种简单的早期诊断工具。我们调查了来自10个有血缘关系的家庭的16名疑似XP患者。采用连锁分析、长程聚合酶链式反应和测序等方法对POLH基因进行分析。遗传分析显示，在所有受影响的患者中，POLH基因与方正单倍型连锁。外显子9至外显子11的长程聚合酶链式反应显示，与对照组相比，外显子9至外显子11有3926个碱基缺失。序列分析表明，这种缺失发生在同一方向的两个Alu-SQ2重复序列之间，分别位于第9和第10内含子。我们推测，这种突变POLHNG 009252.1：G.40771 del3925是由减数分裂时两条同源染色体之间发生的相同交换事件引起的。这些结果使我们能够开发一种基于简单聚合酶链式反应的简单测试，以筛查疑似XP-V患者。在突尼斯，XP-V组的患病率似乎被低估了，临床诊断通常较晚。在XP高发地区，通过聚合酶链式反应对这种创始人突变进行级联筛查，为突尼斯和北非的XP-V早期诊断提供了一种快速且经济有效的工具。
Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG 009252.1: g. 36847 40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.