Disease relevance of BBS1

• Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome [1].
• Bardet-Biedl syndrome (BBS) is a multisystemic disorder characterized by postaxial polydactyly, progressive retinal dystrophy, obesity, hypogonadism, renal dysfunction, and learning difficulty [2].
• CONCLUSIONS: The cardinal feature of retinal degeneration in BBS1 can show a wide spectrum of disease expression [3].
• Renal cancer and malformations in relatives of patients with Bardet-Biedl syndrome [4].
• The ocular manifestations of Bardet-Biedl syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade [5].

Psychiatry related information on BBS1

• Bardet-Biedl syndrome (BBS, OMIM 209900) is a genetic disorder with the primary features of obesity, pigmentary retinopathy, polydactyly, renal malformations, mental retardation and hypogenitalism [1].
• Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism [6].
• Clinical evidence of decreased olfaction in Bardet-Biedl syndrome caused by a deletion in the BBS4 gene [7].

High impact information on BBS1

• Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy [8].
• We then applied this resource to the study of human ciliation disorders and have identified BBS5, a novel gene for Bardet-Biedl syndrome [9].
• We proposed that the pleiotropic phenotype of Bardet-Biedl syndrome (BBS), which encompasses retinal degeneration, truncal obesity, renal and limb malformations and developmental delay, is due to dysfunction of basal bodies and cilia [10].
• Using a bioinformatic screen for ciliary genes in combination with mutational analyses, we identified ARL6 as the gene underlying Bardet-Biedl syndrome type 3, a multisystemic disorder characterized by obesity, blindness, polydactyly, renal abnormalities and cognitive impairment [11].
• We uncovered four different homozygous substitutions in ARL6 in four unrelated families affected with Bardet-Biedl syndrome, two of which disrupt a threonine residue important for GTP binding and function of several related small GTP-binding proteins [11].

Chemical compound and disease context of BBS1

• We report the use of midodrine, an alpha agonist, in an 18-year-old man with Bardet-Biedl syndrome and recurrent intradialytic hypotension [12].

Biological context of BBS1

• Here we report the identification of the gene BBS1 and show that a missense mutation of this gene is a frequent cause of BBS [1].
• The LD data suggest that the BBS1 gene lies in a 1-Mb, sequence-ready region on chromosome 11q13, which should enable its identification [13].
• We use linkage disequilibrium (LD) mapping in an isolated founder population in Newfoundland to significantly reduce the BBS1 critical region [13].
• A founder effect in the newfoundland population reduces the Bardet-Biedl syndrome I (BBS1) interval to 1 cM [13].
• RESULTS: CC-RCC was diagnosed in three of 180 BBS parents and there was loss of heterozygosity at BBS1 (11q13) in the tumour tissue of one of these subjects [4].

Anatomical context of BBS1

• Bardet-Biedl syndrome (BBS) is a pleiotropic genetic disorder with the cardinal features of obesity, photoreceptor degeneration, polydactyly, hypogenitalism, renal abnormalities, and developmental delay [14].
• Liver fibrocystic disease (LFCD), characterized by dilatation of the intrahepatic bile ducts and variable degree of fibrosis, can be present alone or as part of many syndromes, such as Bardet-Biedl syndrome (BBS), Meckel syndrome, Jeune asphyxiating thoracic dysplasia, and Fraser-Jequier-Chen syndrome [15].
• Primary central nervous system lymphoma in a renal transplant recipient with Bardet-Biedl syndrome [16].
• Coupled with recent data on the complex phenotype of Bardet-Biedl syndrome, our findings imply an unexpected central role for basal body and centrosome dysfunction in the pathogenesis of obesity, insulin resistance, and type 2 diabetes [17].
• Furthermore, using somatic hybrid cell hybridization and fluorescence in situ hybridization H-rdgB gene was mapped to human chromosome 11q13, a region known to contain several retinopathy loci, including Best disease and Bardet-Biedl syndrome I. Therefore, H-rdgB gene is an attractive candidate for several inherited retinal degenerative diseases [18].

Associations of BBS1 with chemical compounds

• Empty sellae, impaired testosterone secretion, and defective hypothalamic-pituitary growth and gonadal axes in children with Bardet-Biedl syndrome [19].
• Fluorescence in situ hybridization maps the integrin alpha(11) gene to chromosome 15q23, in the vicinity of an identified locus for Bardet-Biedl syndrome [20].
• Patients with the Bardet-Biedl syndrome should be screened for the presence of abnormalities in glucose metabolism [21].

Other interactions of BBS1

• We identified two novel genes that we initially named "BBS2L1" and "BBS2L2" and that exhibit modest similarity with two discrete, overlapping regions of BBS2 [22].
• However, mutations in MKKS are found in only 4%-11% of unselected Bardet-Biedl syndrome patients [23].
• Evaluation and molecular characterization of EHD1, a candidate gene for Bardet-Biedl syndrome 1 (BBS1) [24].
• McKusick-Kaufman syndrome comprises hydrometrocolpos, polydactyly, and congenital heart defects and overlaps with Bardet-Biedl syndrome, comprising retinitis pigmentosa, polydactyly, obesity, mental retardation, and renal and genital anomalies [23].
• BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance [25].

Analytical, diagnostic and therapeutic context of BBS1

• METHODS: Ten patients (age range, 16-48 years), representing eight pedigrees, with BBS1 gene mutations were studied clinically and with kinetic perimetry, chromatic static perimetry, electroretinography (ERG), and optical coherence tomography [3].
• Linkage mapping in 29 Bardet-Biedl syndrome families confirms loci in chromosomal regions 11q13, 15q22.3-q23, and 16q21 [26].
• Radiation hybrid mapping linked the ISLR gene to AFM248yh1, which is in the critical region of Bardet-Biedl syndrome type 4 (BBS4) on chromosome 15 [27].
• Prenatal diagnosis of Bardet-Biedl syndrome by targeted second-trimester sonography [28].
• Dissection of epistasis in oligogenic Bardet-Biedl syndrome [29].

References