Bardet-Biedl syndrome (BBS) is a rare, developmental disorder characterized by six major symptoms: rod-cone dystrophy, obesity, polydactyly, renal abnormalities, learning difficulties, and hypogonadis Show more
Bardet-Biedl syndrome (BBS) is a rare, developmental disorder characterized by six major symptoms: rod-cone dystrophy, obesity, polydactyly, renal abnormalities, learning difficulties, and hypogonadism. Secondary features include cardiac and hepatic anomalies, metabolic disturbancies, and hearing loss. BBS is genetically heterogeneous with 12 disease genes (BBS1-BBS12) described thus far. Current data suggest a functional disturbance in ciliary function and intraflagellar transport being associated with the phenotype. However, the precise functions of the BBS proteins have yet to be elucidated. This study focuses on the detection of protein factors interacting with BBS proteins. Applying yeast two-hybrid (Y2H) technology we found a series of novel, functionally potentially plausible binding partners of BBS1, BBS2, BBS4, and BBS7. Protein interactions were supported by coimmunoprecipitation analyses (ALDOB, EPAS1) and substantiated by colocalization studies at the subcellular level (ALDOB, EXOC7, FLOT1, KRT18, PAX2). Our work provides new insights into the understanding of BBS interactions and thus their biological function. Show less
Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Bie Show more
Neuromedin B has been shown to exert an inhibiting effect on food consumption in rats. The corresponding gene NMB maps to chromosome 15q22.3-q23, a region expected to contain a gene for the Bardet-Biedl syndrome type 4 (BBS4). Based on its map position and the putative function of the encoded peptide, NMB can be considered as a candidate gene both for BBS4 and the development of human obesity. To examine its involvement in these phenotypes, we determined the genomic structure of human NMB, and performed a mutation screen in its coding region. In genomic DNA of six BBS4 patients and in a large population sample, two sequence variants were detected: a g.253C-->A transversion creating a P73T substitution and a g.401G-->A silent mutation changing the stop codon TGA into stop codon TAA. A case-control study with 92 extremely obese patients and 94 underweight students revealed a significant association between the g.401G-->A polymorphism and body weight (adjustedp = 0.03), which was confirmed in a validation sample consisting of 95 extremely obese patients, and 95 normal weight and 48 underweight individuals (Mann-Whitney p = 0.02). These results suggest a contribution of NMB or a gene in its close vicinity to genetic weight control in humans. Show less