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In this study, we investigated the association of mtDNA variants and haplogroups with Type 2 diabetes (T2D) in Moroccan patients. The Hypervariable Segments 1 of the mtDNA was sequenced in 108 diabetic patients and 97 controls. Association analyses were performed using Fisher’s exact test and multivariate logistic regression. The prevalence of five mtDNA variants (C16187T, C16270T, T16172C, A16293G, and C16320T) was significantly higher in cases than in controls. Among these variants, only C16270T (p = .02) and C16320T (p = .03) remains significant after adjusting by age and gender. We showed that C16270T and C16320T variants were strongly associated with increased risk of T2D in Moroccan patients. [ABSTRACT FROM PUBLISHER]

Objective: Xeroderma pigmentosum (XP) is a genetically and clinically heterogeneous disease, associated with an inherited defect in one of eight different genes (XPA to XPG and XPV). In addition to the early onset of the skin manifestations, the XP group A is marked by the presence of a mild to severe neural disorders which appear tardily and worsens with age. In this study, 9 patients with moderate clinical profile belonging to 6 XP families were recruited to determine the XPA mutational spectrum in Morocco, using the direct sequencing of the whole coding region of the XPA gene. Results: The genetic investigation of the XPA gene showed that 7 from 9 patients were homozygous for the c.682C>T, p.Arg228X mutation, while all their investigated family members were heterozygous. The frequency of this mutation was estimated to be 83.33% (5/6 families). The molecular analysis of the 5 other exons of the XPA gene, showed that the 2 negative siblings carried no mutation in the XPA gene. This finding suggests that c.682C>T (p.Arg228X) mutation is relatively associated with moderate phenotype in XP group A Moroccan families; this result will also contribute to improve the molecular diagnosis of XP disease in Moroccan patients. [ABSTRACT FROM AUTHOR]

Autosomal recessive non-syndromic hearing loss (ARNSHL) is one of the most common genetic diseases in human and is subject to important genetic heterogeneity, rendering molecular diagnosis difficult. Whole-exome sequencing is thus a powerful strategy for this purpose. After excluding GJB2 mutation and other common mutations associated with hearing loss in Morocco, whole-exome sequencing was performed to study the genetic causes of one sibling with ARSHNL in a consanguineous Moroccan family. After filtering data and Sanger sequencing validation, one novel pathogenic homozygous mutation c.1810C > G (p.Arg604Gly) was identified in TMC1 , a gene reported to cause deafness in various populations. Thus, we identified here the first mutation in the TMC1 gene in the Moroccan population causing non-syndromic hearing loss. [ABSTRACT FROM AUTHOR]

Associations with type 2 diabetes mellitus have been identified for variants CDKAL1 rs7756992, KCNJ11 rs5219, and IGF2BP2 rs4402960 in different populations. In a case-control study of 250 unrelated Moroccan diabetic patients and 250 healthy controls, we used TaqMan allelic discrimination assays to genotype the three SNPs and meta-analysis to investigate the association between the polymorphisms and diabetes in Arab populations. The results showed a significant diabetes association only with the variant rs4402960 of the IGF2BP2 gene under additive 2 (GG vs. TT; p = 0.009) and recessive (TT vs. GG+GT; p = 0.003) models. Meta-analysis indicated significant association between the IGF2BP2 rs4402960 and CDKAL1 rs7756992 polymorphisms and increased risk of diabetes in Arab populations. According to our results, the case-control study and meta-analysis revealed a significant association between the IGF2BP2 rs4402960 variant and type 2 diabetes in Moroccan and Arab populations. [ABSTRACT FROM AUTHOR]

Deafness is one of the most common genetic diseases in humans and is subject to important genetic heterogeneity. The most common cause of non syndromic hearing loss (NSHL) is mutations in the GJB2 gene. This study aims to update and evaluate the spectrum of GJB2 allele variants in 152 Moroccan multiplex families with non syndromic hearing loss. Seven different mutations were detected: c.35delG, p.V37I, p.E47X, p.G200R, p.Del120E, p.R75Q, the last three mutations were described for the first time in Moroccan deaf patients, in addition to a novel nonsense mutation, the c.385G>T which is not referenced in any database. Sixty six families (43.42%) have mutations in the coding region of GJB2 , while the homozygous c.35delG mutation still to date the most represented 51/152 (33.55%). The analysis of the geographical distribution of mutations located in GJB2 gene showed more allelic heterogeneity in the north and center compared to the south of Morocco. Our results showed that the GJB2 gene is a major contributor to non syndromic hearing loss in Morocco. Thus, this report of the GJB2 mutations spectrum all over Morocco has an important implication for establishing a suitable molecular diagnosis. [ABSTRACT FROM AUTHOR]

Objectives Autosomal recessive non-syndromic hearing loss is a heterogeneous disorder and the most prevalent human genetic sensorineural defect. In this study, we investigated the geneticcause of sensorineural hearing loss in Moroccan patients and presented the importance of whole exome sequencing (WES) to identify candidate genes in two Moroccan families with profound deafness. Methods After excluding mutations previously reported in Moroccan deaf patients, whole exome sequencing was performed and Sanger sequencing was used to validate mutations in these genes. Results Our results disclosed the c.113_114insT (p.Lys41GlufsX8) and c.406C > T (p.Arg130X) homozygous mutations in PJVK and a homozygous c.5203C > T (p.Arg1735Trp) mutation in MYO15A , both genes responsible for non-syndromic recessive hearing loss DFNB59 and DFNB3, respectively. Conclusion We identified in Moroccan deaf patients two mutations in PJVK and one mutation in MYO15A described for the first time in association with non-syndromic recessive hearing loss. These results emphasize that whole exome sequencing is a powerful diagnostic strategy to identify pathogenic mutations in heterogeneous disorders with many various causative genes. [ABSTRACT FROM AUTHOR]

To decipher and improve the molecular diagnosis of Hypoplastic Amelogenesis Imperfecta in Morocco. Using whole exome sequencing, we analyzed two Moroccan families with Hypoplastic Amelogenesis Imperfecta. The 2 patients from the first family had dental anomalies and short stature syndrome, brachyolmia and nephrocalcinosis with difference in severity, while the proband of the second family had Hypoplastic Amelogenesis Imperfecta with a suspicion of brachyolmia. We identified two novel LTBP3 homozygous variants, the c.2495delT deletion (p.Phe832SerfsTer36) and the c.3716 G>A (p.Cys1239Tyr) missense variant, respectively. Molecular modelling and stability analyses of the missense variant disclosed a possible destabilization of the wild-type structure. Although LTBP3 variants were related to this phenotype in various populations, we report the first LTBP3 variants in the Moroccan population, in families with Hypoplastic Amelogenesis Imperfecta. • Novel LTBP3 variants in Moroccan patients with Hypoplastic Amelogenesis Imperfecta. • Two patients present a nephrocalcinosis in addition to HAI clinical phenotype. • The c.3716 G>A missense variant destabilizes LTBP3 wild-type structure. [ABSTRACT FROM AUTHOR]