Molecular Investigation of Genetic Orphan Diseases Research Unit, Pasteur Institute of Tunis, Tunis, Tunisia.
Int J Dermatol. 2010 May;49(5):544-8. doi: 10.1111/j.1365-4632.2010.04421.x.
Xeroderma Pigmentosum (XP) is a rare autosomal recessive disorder characterized by cutaneous and ocular alterations. Eight genes, Xeroderma Pigmentosum group A (XPA) to Xeroderma Pigmentosum group G (XPG) and Xeroderma Pigmentosum group V (XPV), are known to be responsible for the disease and products of these genes are involved in the repair of deoxyribonucleic acid (DNA) lesions generated by UV radiation. Several XP patients suffer from neurological defects, found in the XPA (the most common form), D and G groups. The aim of this study was to investigate the mutational spectrum of XPA in Tunisia, in order to propose a simple tool for molecular diagnosis.
This study was carried out on six unrelated families with nine Tunisian XPA patients. Clinical features were recorded. As a previous study showed the presence of the R228X mutation in Tunisia, patients were first screened for this mutation by polymerase chain reaction-restriction fragment length polymorphism and then confirmed by direct sequencing.
The results showed that all patients carried the XPA R228X mutation. This mutation corresponds to a C to T transition, which creates a premature stop codon at position 228, thus causing a DNA repair defect.
The XPA R228X mutation is common in Tunisian population. This mutation is associated with a relatively moderate phenotype of the XPA. As all explored patients presented the recurrent mutation XPA R228X, a potential founder effect was searched and confirmed by haplotype analysis. Taking into account similar genetic background, investigation of this mutation should allow a cost effective and rapid diagnosis of XPA in north-African populations.
着色性干皮病（XP）是一种罕见的常染色体隐性遗传疾病，其特征为皮肤和眼部改变。已知有 8 个基因，即 XP 组 A（XPA）至 XP 组 G（XPG）和 XP 组 V（XPV），负责该疾病，这些基因的产物参与修复由紫外线辐射引起的脱氧核糖核酸（DNA）损伤。一些 XP 患者患有神经系统缺陷，在 XPA（最常见的形式）、D 和 G 组中发现。本研究旨在调查突尼斯 XPA 的突变谱，以便提出一种简单的分子诊断工具。
本研究在六个不相关的家庭中进行，有 9 名突尼斯 XPA 患者。记录临床特征。由于之前的研究表明突尼斯存在 R228X 突变，因此患者首先通过聚合酶链反应-限制性片段长度多态性进行该突变的筛查，然后通过直接测序进行确认。
结果显示，所有患者均携带 XPA R228X 突变。该突变对应于 C 到 T 的转换，在位置 228 处产生一个过早的终止密码子，从而导致 DNA 修复缺陷。
XPA R228X 突变在突尼斯人群中很常见。该突变与 XPA 的相对中度表型相关。由于所有探索的患者均携带反复出现的 XPA R228X 突变，因此通过单体型分析搜索并确认了潜在的创始效应。考虑到类似的遗传背景，对该突变的研究应允许在北非人群中进行经济有效的快速 XPA 诊断。
