Kallabi Fakhri, Ben Rebeh Imen, Felhi Rahma, Sellami Dorra, Masmoudi Saber, Keskes Leila, Kamoun Hassen
Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia.
Horm Res Paediatr. 2016;85(1):18-21. doi: 10.1159/000441653. Epub 2015 Nov 24.
BACKGROUND/AIMS: Allgrove syndrome is a rare autosomal recessive disorder characterized by alacrima, achalasia, and adrenal insufficiency. It is caused by mutations of the AAAS gene located on chromosome 12q13 encoding the WD-repeat protein ALADIN. The c.1331+1G>A mutation is one of the most common mutations described in the literature and was identified in Tunisian and Algerian populations. Herein, we describe the clinical and genetic profile of two families from Libya in North Africa associated with Allgrove syndrome.
Two unrelated families clinically diagnosed with Allgrove syndrome were evaluated for sequence variations in the AAAS gene. Blood samples were collected, and isolated DNA derived from the subjects was amplified. The entire sequence of the AAAS gene was analyzed by PCR-RFLP and direct sequencing.
Molecular analysis revealed the major homozygous mutation (c.1331+1G>A) in all patients. The presence of a major mutation in Tunisia, Algeria and, as discovered in this report, in Libya in patients with Allgrove syndrome suggests the existence of an ancestral mutation and a founder effect in North Africa.
The findings allow for a fast genetic counseling in North African families with Allgrove syndrome. To the best of our knowledge, this is the first report of Allgrove syndrome in Libya.
背景/目的：奥尔格罗夫综合征是一种罕见的常染色体隐性疾病，其特征为无泪、贲门失弛缓症和肾上腺功能不全。它由位于12q13染色体上的AAAS基因突变引起，该基因编码WD重复蛋白ALADIN。c.1331+1G>A突变是文献中描述的最常见突变之一，在突尼斯和阿尔及利亚人群中被发现。在此，我们描述了来自北非利比亚的两个与奥尔格罗夫综合征相关家族的临床和基因概况。
对两个临床诊断为奥尔格罗夫综合征的无关家族进行AAAS基因序列变异评估。采集血样，对受试者分离出的DNA进行扩增。通过PCR-RFLP和直接测序分析AAAS基因的完整序列。
分子分析显示所有患者均存在主要纯合突变（c.1331+1G>A）。在突尼斯、阿尔及利亚以及本报告中发现的利比亚的奥尔格罗夫综合征患者中存在主要突变，这表明在北非存在一个祖先突变和奠基者效应。
这些发现有助于对北非患有奥尔格罗夫综合征的家族进行快速的遗传咨询。据我们所知，这是利比亚关于奥尔格罗夫综合征的首次报告。
