| Summary: | Thesis (M.Sc.)--Memorial University of Newfoundland, 2009. Medicine Includes bibliographical references (leaves 70-81) Bardet-Biedl Syndrome (BBS) is an autosomal recessive, genetically heterogenous, ciliopathic condition, characterized by dystrophic extremities, retinal dystrophy, obesity, renal abnormalities and male hypogonadism. It is possible that inheritance of a single BBS mutation may predispose to complex diseases such as obesity, hypertension and diabetes, particularly as these disorders occur frequently in BBS. To determine the incidence of metabolic and renal events 46 BBS cases, 96 heterozygote BBS mutation carriers, and 37 relatives without a BBS mutation were studied. Cases have been followed prospectively for up to 28 years, but relatives were assessed for the first time. -- The molecular basis of BBS was identified in all families in whom DNA was obtained: 9 mutations in 6 different BBS genes were discovered in 21 families. Body mass index in adult cases was 38 ± 12, in carriers 28 ± 6 and in non carriers 29 ± 3. Hypertension had developed in 72% of cases, in 54% of carriers and 49% of non carriers. Median time to onset of hypertension treatment was 34, 63 and 67 years respectively. Diabetes had developed in 50% of cases, 17% of carriers, and 24% of non carriers, with median time to diabetes being 43, 75 years and not achieved respectively. Stage 3 chronic kidney disease had developed in 47% of cases, 11% of carriers, 15% of non carriers, with median age to diagnosis being 58, 86 and 81 years respectively. -- Metabolic and renal events occurred frequently and at an early age in BBS. There were no significant differences in the risk of these events comparing carriers of a BBS mutation to non carriers. Inheritance of a BBS mutation does not predispose to obesity, diabetes, hypertension or renal impairment.
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