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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Genetic exclusion of 14 candidate genes in lipoatropic diabetes using linkage analysis in 10 consanguineous families.
Journal of Clinical Endocrinology and Metabolism 1997 October
Lipoatropic diabetes (LD) is a rare recessive autosomal disorder, mainly characterized by lipoatrophy with alterations in lipid metabolism and extreme insulin resistance. To identify molecular defects responsible for this disease, we tested the implication of 14 candidate genes coding for proteins involved either in insulin action, i.e. insulin receptor, insulin receptor substrate 1, insulin-like growth factor I receptor, diabetes-associated ras-like protein (Rad), and glycogen synthase, or in lipid metabolism, i.e. lipoprotein lipase; apolipoproteins CII, AII, and CIII; hepatic lipase; hormone-sensitive lipase; the beta 3-adrenergic receptor; leptin; and fatty acid-binding protein 2. To this end, haplotype and linkage analyses using genotyping with microsatellites in 10 consanguineous families provided us with powerful genetic tools. Our results show that in most families, lod scores at a null recombination fraction were less than -2. Haplotype analysis also argues against the involvement of these genes in LD. This implies that mutations in these genes are unlikely to make a major genetic contribution to LD.
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