Department of Histology and Cytogenetics, Institut Pasteur de Tunis Tunis, Tunisia ; Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
Laboratory of Biomedical Genomics and Oncogenetics, Institut Pasteur de Tunis, Tunis El Manar University Tunis, Tunisia.
Mol Genet Genomic Med. 2014 Mar;2(2):160-5. doi: 10.1002/mgg3.55. Epub 2014 Feb 5.
Tunisian population is characterized by its heterogeneous ethnic background and high rate of consanguinity. In consequence, there is an increase in the frequency of recessive genetic disorders including Fanconi anemia (FA). The aim of this study was to confirm the existence of a founder haplotype among FA Tunisian patients and to identify the associated mutation in order to develop a simple tool for FA diagnosis. Seventy-four unrelated families with a total of 95 FA patients were investigated. All available family members were genotyped with four microsatellite markers flanking FANCA gene. Haplotype analysis and homozygosity mapping assigned 83 patients belonging to 62 families to the FA-A group. A common haplotype was shared by 42 patients from 26 families at a homozygous state while five patients from five families were heterozygous. Among them, 85% were from southern Tunisia suggesting a founder effect. Using multiplex ligation-dependent probe amplification (MLPA) technique, we have also demonstrated that this haplotype is associated with a total deletion of exon 15 in FANCA gene. Identification of a founder mutation allowed genetic counseling in relatives of these families, better bone marrow graft donor selection and prenatal diagnosis. This mutation should be investigated in priority for patients originating from North Africa and Middle East.
突尼斯人口的特点是其多样化的民族背景和高近亲结婚率。因此，隐性遗传疾病的频率增加，包括范可尼贫血（FA）。本研究的目的是确认 FA 突尼斯患者中是否存在一个起始单倍型，并确定相关突变，以便开发一种简单的 FA 诊断工具。对 74 个无血缘关系的家庭进行了研究，共 95 个 FA 患者。用四个微卫星标记侧翼 FANCA 基因对所有可用的家庭成员进行了基因分型。单体型分析和纯合性作图将属于 62 个家庭的 83 名患者分配到 FA-A 组。一个常见的单体型在 26 个家庭的 42 名患者中以纯合状态共享，而 5 名患者来自 5 个家庭为杂合状态。其中 85%来自突尼斯南部，提示存在起始突变。使用多重连接依赖性探针扩增（MLPA）技术，我们还证明了这种单体型与 FANCA 基因外显子 15 的完全缺失有关。发现一个起始突变，可以对这些家庭的亲属进行遗传咨询、更好地选择骨髓供体和进行产前诊断。这种突变应优先在来自北非和中东的患者中进行调查。
