Ben Halim Nizar, Dorboz Imen, Kefi Rym, Kharrat Najla, Eymard-Pierre Eleonore, Nagara Majdi, Romdhane Lilia, Ben Alaya-Bouafif Nissaf, Rebai Ahmed, Miladi Najoua, Boespflug-Tanguy Odile, Abdelhak Sonia
Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002, Tunis, Belvédère, Tunisia.
Child Neurological Diseases Unit, Faculty of Medicine, 1007, Tunis, Tunisia.
Neurol Sci. 2016 Mar;37(3):403-9. doi: 10.1007/s10072-015-2417-5. Epub 2015 Nov 14.
Arylsulfatase A (ASA) is a lysosomal enzyme involved in the catabolism of cerebroside sulfate. ASA deficiency is associated with metachromatic leukodystrophy (MLD). Low ASA activities have also been reported in a more common condition with no apparent clinical consequences termed ASA pseudo-deficiency (ASA-PD) which is associated with two linked mutations in the ASA gene (c.1049A>G and c.*96A>G). This study aimed to investigate the frequency of the two ASA-PD variants and their linkage disequilibrium (LD) among Tunisians. ASA-PD variants were detected in 129 healthy Tunisians and their frequencies were compared to those described worldwide. The frequency of the PD allele was estimated at 17.4% for the overall sample, with c.1049A>G and c.*96A>G frequencies of 25.6 and 17.4%, respectively. This study also revealed a high LD between the two ASA-PD variants (r(2) = 0.61). Inter-population analysis revealed similarities in the ASA-PD genetic structure between Tunisians and populations from Middle East with c.*96A>G frequencies being the highest in the world. A significant North vs. South genetic differentiation in the ASA-PD frequency was also observed in Tunisian population who seems genetically intermediate between Africans, Middle-Easterners and Europeans. This is the first report on the allele frequency of the ASA-PD in North Africa, revealing a relatively high frequency of the PD allele among Tunisians. This study gives also evidence on the importance of discriminating ASA-PD allele from pathological mutations causing MLD and supporting enzymatic activity testing with both sulfatiduria determination and genetic testing in the differential diagnosis of MLD in the Tunisian population.
芳基硫酸酯酶A（ASA）是一种参与硫酸脑苷脂分解代谢的溶酶体酶。ASA缺乏与异染性脑白质营养不良（MLD）相关。在一种更常见的、无明显临床后果的情况（称为ASA假性缺乏，ASA-PD）中也报告了低ASA活性，其与ASA基因中的两个连锁突变（c.1049A>G和c.*96A>G）相关。本研究旨在调查突尼斯人中这两种ASA-PD变体的频率及其连锁不平衡（LD）情况。在129名健康突尼斯人中检测到了ASA-PD变体，并将其频率与全球报道的频率进行了比较。总体样本中PD等位基因的频率估计为17.4%，c.1049A>G和c.*96A>G的频率分别为25.6%和17.4%。本研究还揭示了两种ASA-PD变体之间存在高度的LD（r(2)=0.61）。群体间分析显示，突尼斯人与中东人群在ASA-PD基因结构上具有相似性，c.*96A>G的频率在世界上是最高的。在突尼斯人群中还观察到ASA-PD频率存在显著的南北遗传分化，突尼斯人在基因上似乎处于非洲人、中东人和欧洲人之间。这是关于北非ASA-PD等位基因频率的首次报告，揭示了突尼斯人中PD等位基因的频率相对较高。本研究还证明了在突尼斯人群中鉴别ASA-PD等位基因与导致MLD的病理性突变的重要性，并支持在MLD的鉴别诊断中通过硫酸脑苷脂尿测定和基因检测进行酶活性测试。
