Determination of arylsulfatase A pseudodeficiency allele and haplotype frequency in the Tunisian population

Nizar Ben Halim 1 Imen Dorboz 2, 3 Rym Kefi 1 Najla Kharrat 4 Eléonore Eymard-Pierre 5, 6 Majdi Nagara 1 Lilia Romdhane 1 Nissaf Ben Alaya-Bouafif 7 Ahmed Rebai 4 Najoua Miladi 3 Odile Boespflug-Tanguy 8, 9, 10 Sonia Abdelhak 1
1 LR11IPT05 - Laboratoire de Génomique Biomédicale et Oncogénétique
2 Physiopathologie et neuroprotection des atteintes du cerveau en développement
3 Child Neurological Diseases Unit
4 Bioinformatics and Biostatistics [Sfax]
5 CHU Clermont-Ferrand
6 GReD - Génétique, Reproduction et Développement - Clermont Auvergne
7 Laboratoire d'Epidémiologie et d'Ecologie parasitaire, Institut Pasteur de Tunis
8 Centre de référence des leucodystrophies
9 INSERM - Institut National de la Santé et de la Recherche Médicale
10 UPD7 - Université Paris Diderot - Paris 7
Abstract : 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.
Keywords : Haplotype analysis Genetic polymorphism Arylsulfatase A pseudo-deficiency Linkage disequilibrium Tunisia Genetic differentiation
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Article dans une revue
Neurological Sciences, Springer Verlag, 2016, 37 (3), pp.403-409. 〈10.1007/s10072-015-2417-5〉
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https://hal-riip.archives-ouvertes.fr/pasteur-01374976
Contributeur : Institut Pasteur Tunis <>
Soumis le : mardi 6 décembre 2016 - 14:07:45
Dernière modification le : lundi 5 février 2018 - 15:22:13

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Nizar Ben Halim, Imen Dorboz, Rym Kefi, Najla Kharrat, Eléonore Eymard-Pierre, et al.. Determination of arylsulfatase A pseudodeficiency allele and haplotype frequency in the Tunisian population. Neurological Sciences, Springer Verlag, 2016, 37 (3), pp.403-409. 〈10.1007/s10072-015-2417-5〉. 〈pasteur-01374976〉

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