Triallelic Inheritance in Bardet-Biedl Syndrome, a Mendelian Recessive Disorder

作者：Nicholas Katsanis, Stephen J. Ansley, José Luis Badano, Erica R. Eichers, Richard Alan Lewis, Bethan E. Hoskins, Peter James Scambler, William S. Davidson, Philip L. Beales, James R. Lupski · 发表于：Science · 年份：2001 · DOI：10.1126/science.1063525 · 被引用次数：668 · 研究领域：Genetic and Kidney Cyst Diseases、Genetic Syndromes and Imprinting、Hedgehog Signaling Pathway Studies

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder characterized by multiple clinical features that include pigmentary retinal dystrophy, polydactyly, obesity, developmental delay, and renal defects. BBS is considered an autosomal recessive disorder, and recent positional cloning efforts have identified two BBS genes (BBS2 and BBS6). We screened our cohort of 163 BBS families for mutations in both BBS2 and BBS6 and report the presence of three mutant alleles in affected individuals in four pedigrees. In addition, we detected unaffected individuals in two pedigrees who carry two BBS2 mutations but not a BBS6 mutation. We therefore propose that BBS may not be a single-gene recessive disease but a complex trait requiring three mutant alleles to manifest the phenotype. This triallelic model of disease transmission may be important in the study of both Mendelian and multifactorial disorders.