WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon

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dc.contributor.author Zallloua, Pierre A.
dc.contributor.author Azar, Sami T.
dc.contributor.author Delepine, Marc
dc.contributor.author Makhoul, Nadine J.
dc.contributor.author Blanc, Herve
dc.contributor.author Sanyoura, May
dc.contributor.author Lavergne, Anne
dc.contributor.author Stankov, Karmen
dc.contributor.author Lemainque, Arnaud
dc.contributor.author Baz, Patrick
dc.contributor.author Julier, Cecile
dc.date.accessioned 2019-07-25T08:36:23Z
dc.date.available 2019-07-25T08:36:23Z
dc.date.copyright 2008 en_US
dc.date.issued 2019-07-25
dc.identifier.issn 1460-2083 en_US
dc.identifier.uri http://hdl.handle.net/10725/11142
dc.description.abstract Most cases of juvenile-onset diabetes (JOD) are diagnosed as type 1 diabetes (T1D), for which genetic studies conducted in outbred Caucasian populations support the concept of multifactorial inheritance. However, this view may be partly challenged in particular population settings. In view of the suggestive evidence for a high prevalence of Wolfram syndrome (WFS) in Lebanon, the phenotypic variability associated with WFS1 mutations, and the high consanguinity rate in Lebanon, we aimed to evaluate the contribution of WFS1 mutations as monogenic determinants to JOD in Lebanon. We performed a family-based genetic study, with linkage analysis followed by systematic mutation screening of WFS1 exons in all JOD probands. The study population consisted of an unbiased recruitment of all juvenile-onset insulin-dependent diabetic patients from a specialized diabetes pediatric clinic in Beirut, Lebanon. Homozygous or compound heterozygous WFS1 mutations were found in 22 of the 399 JOD probands (5.5%), resulting in WFS (17 probands) or in non-syndromic non-autoimmune diabetes mellitus (DM, five probands). These accounted for 12.1% (21/174) of probands in consanguineous families, compared with 0.4% (1/225) in non-consanguineous families. Of the 38 patients identified with homozygous or compound heterozygous WFS1 mutations, 11 (29%) had non-syndromic DM, all of whom carried a particular WFS1 mutation, WFS1LIB, encoding a protein with an extended C-terminal domain. This mutation resulted in a delayed onset or absence of extrapancreatic features. These results underscore the major impact of population-specific factors, such as population-specific mutations and founder effects, and family structure in the genetic determinism of JOD. en_US
dc.language.iso en en_US
dc.title WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon en_US
dc.type Article en_US
dc.description.version Published en_US
dc.author.school SOM en_US
dc.author.idnumber 20030001 en_US
dc.author.department N/A en_US
dc.description.embargo N/A en_US
dc.relation.journal Human Molecular Genetics en_US
dc.journal.volume 17 en_US
dc.journal.issue 24 en_US
dc.article.pages 4012-4021 en_US
dc.keywords Diabetes mellitus en_US
dc.keywords Mutation en_US
dc.keywords Diabetes mellitus en_US
dc.keywords Type 1 en_US
dc.keywords Heterozygote en_US
dc.keywords Homozygote en_US
dc.keywords Lebanon en_US
dc.keywords Proband en_US
dc.identifier.doi https://doi.org/10.1093/hmg/ddn304 en_US
dc.identifier.ctation Zalloua, P. A., Azar, S. T., Delépine, M., Makhoul, N. J., Blanc, H., Sanyoura, M., ... & Julier, C. (2008). WFS1 mutations are frequent monogenic causes of juvenile-onset diabetes mellitus in Lebanon. Human molecular genetics, 17(24), 4012-4021. en_US
dc.author.email pierre.zalloua@lau.edu.lb en_US
dc.identifier.tou http://libraries.lau.edu.lb/research/laur/terms-of-use/articles.php en_US
dc.identifier.url https://academic.oup.com/hmg/article/17/24/4012/559201 en_US
dc.orcid.id https://orcid.org/0000-0002-8494-5081 en_US
dc.author.affiliation Lebanese American University en_US

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