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

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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.

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Acknowledgments

The authors are grateful to all volunteers who kindly accepted to be enrolled in this study. The authors would also like to thank Meherzia Ben Fadhel, Sonia Chakroun and Sihem Ben Fadhel for their help in collecting material and for their skilful technical assistance.

This work was supported by the Ministry of Higher Education and Scientific Research and by the Ministry of Health.

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Authors and Affiliations

  1. Laboratoire de Génomique Biomédicale et Oncogénétique, Institut Pasteur de Tunis, BP 74, 13 Place Pasteur, 1002, Tunis, Belvédère, Tunisia

    Nizar Ben Halim, Rym Kefi, Majdi Nagara, Lilia Romdhane & Sonia Abdelhak

  2. Child Neurological Diseases Unit, Faculty of Medicine, 1007, Tunis, Tunisia

    Imen Dorboz & Najoua Miladi

  3. INSERM U676, 75935, Paris Cedex 19, France

    Imen Dorboz & Odile Boespflug-Tanguy

  4. Bioinformatics Unit, Centre of Biotechnology of Sfax, 3018, Sfax, Tunisia

    Najla Kharrat & Ahmed Rebai

  5. Faculté de Médecine, INSERM UMR 931, GReD, 63000, Clermont-Ferrand, France

    Eleonore Eymard-Pierre

  6. Department of Genetics and Cytogenetics, CHU de Clermont-Ferrand, 63003, Clermont-Ferrand Cedax 1, France

    Eleonore Eymard-Pierre

  7. Laboratory of Epidemiology, Institut Pasteur de Tunis, 1002, Tunis, Tunisia

    Nissaf Ben Alaya-Bouafif

  8. Assistance Publique des Hôpitaux de Paris (APHP), Centre de Reference « leucodystrophies », Hôpital Robert Debré, 75019, Paris, France

    Odile Boespflug-Tanguy

  9. Université Paris Diderot, Sorbonne Paris Cité, 75205, Paris Cedex 13, France

    Odile Boespflug-Tanguy

Authors
  1. Nizar Ben Halim
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  2. Imen Dorboz
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  3. Rym Kefi
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  6. Majdi Nagara
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  7. Lilia Romdhane
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  8. Nissaf Ben Alaya-Bouafif
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  9. Ahmed Rebai
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  11. Odile Boespflug-Tanguy
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  12. Sonia Abdelhak
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Correspondence to Nizar Ben Halim.

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Ben Halim, N., Dorboz, I., Kefi, R. et al. Determination of arylsulfatase A pseudodeficiency allele and haplotype frequency in the Tunisian population. Neurol Sci 37, 403–409 (2016). https://doi.org/10.1007/s10072-015-2417-5

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  • DOI: https://doi.org/10.1007/s10072-015-2417-5

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