Research Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Department of Biology, Laboratory of Biotechnologies and Valorization of Natural Resources, School of Sciences, IBN Zohr University, Agadir, Morocco.
BMC Genomics. 2024 Oct 9;25(1):948. doi: 10.1186/s12864-024-10724-1.
Mucopolysaccharidosis type I is a lysosomal storage disease resulting from a deficiency in alpha-L-iduronidase (IDUA), which causes the accumulation of partially degraded dermatan sulfate and heparan sulfate. This retrospective study, spanning eight years, analyzed data from 45 MPSI patients. The report aimed to explore the potential origin of the p.P533R mutation in the Maghrebin population by constructing a single-nucleotide polymorphism haplotype around the IDUA gene, in order to propose a molecular proof of a founder effect of the MPSI/p.P533R allele.
All of the studied patients were from Libya (2), Mauritania (1) Morocco (21) and Tunisia (21) with first cousins being the most frequent union. The diagnosis of MPSI patients often involves the combination of urinary screening, leukocyte IDUA activity determination, and DNA molecular analysis. In our study, to identify the common p.P533R mutation, we performed both DNA sequencing and tetra-primer ARMS PCR assay. Additionally, Haploview was used to determine the specific haplotype that cosegregates with the p.P533R mutation. Controls were genotyped to ensure that all the SNPs were in Hardy-Weinberg equilibrium.
In the present report we confirmed the very strong impact of consanguinity on the incidence of MPSI disease. Furthermore, studied families of mixed ancestry shared common and specific haplotype, which was observed in studied populations, suggesting the presence of a founder effect in the North Africa.
The p.P533R missense mutation was identified in each patient originated from Libya, Mauritania, Morocco and Tunisia. Furthermore, these MPSI patients exhibited the same IDUA haplotype. The occurrence of a shared AAGGGTG haplotype, among North African populations may be attributed to substantial historical gene exchange between these groups, likely stemming from migration, inter-ethnic marriage, or other forms of interaction throughout history.
黏多糖贮积症 I 型是一种溶酶体贮积病，由α-L-艾杜糖苷酸酶（IDUA）缺乏引起，导致部分降解的硫酸皮肤素和硫酸乙酰肝素的积累。这项为期八年的回顾性研究分析了 45 名 MPSI 患者的数据。本报告旨在通过构建 IDUA 基因周围的单核苷酸多态性单倍型，探讨 Maghrebin 人群中 p.P533R 突变的潜在起源，以便提出 MPSI/p.P533R 等位基因的奠基者效应的分子证据。
所有研究患者均来自利比亚（2 例）、毛里塔尼亚（1 例）、摩洛哥（21 例）和突尼斯（21 例），其中最常见的亲缘关系是表亲。MPSI 患者的诊断通常涉及尿筛查、白细胞 IDUA 活性测定和 DNA 分子分析的结合。在我们的研究中，为了鉴定常见的 p.P533R 突变，我们同时进行了 DNA 测序和四引物 ARMS-PCR 检测。此外，Haploview 用于确定与 p.P533R 突变共分离的特定单倍型。对照进行基因分型以确保所有 SNP 均处于 Hardy-Weinberg 平衡状态。
本报告证实了近亲结婚对 MPSI 疾病发生率的巨大影响。此外，具有混合血统的研究家族共享共同和特定的单倍型，这在研究人群中观察到，表明在北非存在奠基者效应。
在来自利比亚、毛里塔尼亚、摩洛哥和突尼斯的每位患者中均发现了 p.P533R 错义突变。此外，这些 MPSI 患者表现出相同的 IDUA 单倍型。在北非人群中，共同的 AAGGGTG 单倍型的发生可能归因于这些群体之间历史上大量的基因交换，这种交换可能源于移民、族际通婚或历史上的其他形式的互动。
