Molecular analysis in a GALNS study cohort of 15 Tunisian patients: description of a novel mutation
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RESEARCH
Open Access
Molecular analysis in a GALNS study cohort of 15 Tunisian patients: description of a novel mutation Latifa Chkioua1,2, Souhir Khedhiri1,2, Hind Hafsi3, Oussama Grissa1, Hadhami Ben Turkia4, Abdelhedi Miled1,2, Sandrine Laradi5, Roseline Froissart6 and Najat Alif7*
Abstract Background: Mucopolysaccharidosis type IVA (MPS IVA) is an autosomal recessive disease caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS). The purpose of this study was to analyze the GALNS mutations and the haplotypes associated. Methods: Mutation screening of the GALNS gene was performed by direct sequence analysis using DNA samples from 15 unrelated Tunisian MPS IVA patients. We also analyzed the haplotypes associated with the novel mutation and with the other reported GALNS mutations. Results: We have identified an unreported missense mutation p.D288G (c.863A > G) in one patient, the most frequently c.120 + 1G > A (IVS1 + 1G > A) mutation in eleven MPS IVA patients and three previously reported mutations p.G66R, p.A85T and p.R386C on the other MPS IVA patients. All the studied patients were homozygous for these identified mutations. Bioinformatics analysis predicted the novel mutation as being probably pathogenic. These findings with the unobserved p.D288G mutation in controls subjects, suggested that it is a disease-causing mutation, which was correlated with the severe phenotype observed in the patients. We have found that the two GALNS unreported and reported mutations, respectively p.D288G and p.R386C, were associated with a common and specific haplotype. Conclusion: Our results were in agreement with previous reports from Tunisia, suggesting, on one hand the genotype/phenotype correlations in MPS IVA patients and the other hand the haplotype analyses were useful for determination of mutation origin in Tunisian population. Keywords: Mucopolysaccharidosis type IVA, N-acetylgalactosamine-6-sulfatase, Mutation screening, Bioinformatics analysis, Haplotypes Résumé: La mucopolysccharidose de type IV A (MPS IVA) est une maladie autosomique récessive due à la déficience de l’enzyme lysosomale N-acétylgalactosamine-6-sulfate sulfatase (GALNS). Le but de cette étude est d’analyser les mutations du gène GALNS et les haplotypes associés. Méthodes: Le dépistage des mutations dans le gène GALNS a été réalisé par l’analyse directe des séquences en utilisant des échantillons d’ADN issus de 15 patients non apparentés atteints de la MPS IVA. Par ailleurs, nous avons analysé les haplotypes associés, d’une part à la mutation nouvelle, et d’autre part, aux autres mutations déjà rapportées. (Continued on next page)
* Correspondence: [email protected] 7 Department of Biology, Laboratory of Biotechnologies and Valorization of Natural Resources. IBN Zohr University, School of Sciences, BP 8106 Agadir, Morocco Full list of author information is available at the end of the article © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution
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