HB S [beta 6(A3)GLU -> VAL, GAG > GTG] AND beta-GLOBIN GENE CLUSTER HAPLOTYPE DISTRIBUTION IN MAURITANIA

International audienceOf 1050 Mauritanian blood donors screened from the two main racial groups, i.e., the Moors and Black Africans, 60 were found to carry Hb S [beta 6(A3) Glu -> Val, GAG>GTG], giving a global frequency of 5.71%. The prevalence observed in the Black African Mauritanians (10.69%) is almost five times that found in the Moor group (2.25%). Four of the five main beta(S) haplotypes were detected in this study: Senegal (77.8%), Benin (8.8%), Arab-Indian (5.5%) and Bantu (4.4%). These data showed that Hb S is a serious public health problem in Mauritania. They also confirm the ethnic heterogeneity of the Mauritanian population

Identification a novel pathogenic LRTOMT mutation in Mauritanian families with nonsyndromic deafness

International audiencePurposeAlthough recessive mutations in GJB2 are the common genetic etiology of sensorineural hearing impairment (SNHI), variants in LRTOMT gene were also identified, mostly in Middle East and North African populations.MethodsUsing Sanger sequencing we screened the exon 7 of LRTOMT in a cohort of 128 unrelated Mauritanian children with congenital deafness.ResultsOnly one biallelic missense mutation, predicted as pathogenic (c.179 T > C;p.Leu60Pro) was found at homozygous state in four families. This variant, not reported before, showed a deleterious effect by SIFT (score: 0.01) and a disease-causing effect by Mutation Taster (prob: 1). Exploration of the encoded protein 3D structure revealed a disruption from an organized α helix (in the normal protein structure) into a random conformation. Early fitting of a cochlear implant seemed to improve the audition ability of the mutation carrier.ConclusionFurther screening using a panel of deafness genes may expose other variants underlying hearing impairment in our population

Type 2 diabetes in Mauritania: Prevalence of the undiagnosed diabetes, influence of family history and maternal effect

International audienceAim: We estimated the prevalence of undiagnosed diabetes, analyzed the influence of family history on the occurrence of T2D and evaluated its aggregation pattern in the Mauritanian population. Methods: The prevalence of unknown diabetes was obtained using data compiled from 1278 Mauritanian adults applying a questionnaire and fasting serum glucose tests. Detailed family history of diabetes and clinical characteristics were gathered from 421 T2D patients. Results: The prevalence of undiagnosed diabetes was 4.7 +/- 1.2% in the studied population (3.1% in men and 6.4% in women). 27% of T2D patients reported at least one relative with diabetes. Association between family history and diabetes was higher among first degree compared to second degree relatives (p = 0.003). We observed more probands with an affected mother than those who have a father with diabetes (p = 0.002), suggesting a preferential maternal effect which did not extend to second degree relatives. Conclusions: These results show that the prevalence of diabetes in the Mauritanian population could be higher than currently thought. Family history screening may be used in the management of this condition in Mauritania. (C) 2012 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved

A novel missense mutation of GJA8 causes congenital cataract in a large Mauritanian family

International audienceOBJECTIVE OF THE STUDY: Inborn lens opacity is the most frequent cause of childhood blindness. In this study, we aimed to define the presumed genetic cause of a congenital cataract present in a Mauritanian family over the last nine generations.METHODS: A family history of the disease and eye examination were carried out for the family members. Next-generation sequencing using a panel of 116 cataract underlying genes was selectively conducted on the proband's DNA. Nucleotide and amino acid changes and their impact on the phenotype were evaluated using various data analyzing software.RESULTS: Congenital nuclear cataract, with autosomal dominant mode, was observed in the family. All patients had consequences on their vision in the first 2 years of life. Genetic screening revealed a new mutation c.166A>C (p.Thr56Pro) in GJA8, encoding the Cx50 α-connexin protein. This mutation co-segregated in all patients and was not observed in the unaffected family members and controls. The predicted secondary structure impacted by p.Thr56Pro revealed a localized disruption, in the first extra membrane loop of the wild-type sheet, which is replaced in the mutant protein by a turn then a coil. This conformational change was functionally predicted as probably damaging.CONCLUSION: A new mutation (c.166A>C) in GJA8 underlying a nuclear congenital cataract was identified in this study. Its segregation with the phenotype might be useful as a predicting marker of the disease

Mutation profile of glaucoma candidate genes in Mauritanian families with primary congenital glaucoma.

International audiencePurpose: Intraocular pressure leading to glaucoma is a major cause of childhood blindness in developing countries. In this study, we sought to identify gene variants potentially associated with primary congenital glaucoma (PCG) in the Mauritanian population.Methods: Using next-generation sequencing (NGS), a panel of PCG candidate genes was screened in a search for DNA mutations in four families with multiple occurrences of PCG.Results: Targeted exome sequencing analysis revealed predicted pathogenic mutations in four genes: CYP1B1 (c.217_218delTC, p.Ser73Valfs*150), MYOC (878C>A, p.T293K), NTF4 (c.601T>G, p.Cys201Gly), and WDR36 (c.2078A>G, p.Asn693Ser), each carried by a different family.Conclusions: Genetic variation associated with PCG in this study reflects the ethnic heterogeneity of the Mauritanian population. However, a larger cohort is needed to identify additional families carrying these mutations and confirm their biologic role