Disease relevance of BBS4

• Identification of the gene that, when mutated, causes the human obesity syndrome BBS4 [1].
• CONCLUSIONS: The phenotype of patients with BBS4 mutations consists of severe retinitis pigmentosa, variable obesity, brachydactyly with variable polydactyly, small or missing teeth, genital hypoplasia, and cardiovascular disease [2].

Psychiatry related information on BBS4

• Clinical evidence of decreased olfaction in Bardet-Biedl syndrome caused by a deletion in the BBS4 gene [3].

High impact information on BBS4

• Here we show that BBS4 localizes to the centriolar satellites of centrosomes and basal bodies of primary cilia, where it functions as an adaptor of the p150(glued) subunit of the dynein transport machinery to recruit PCM1 (pericentriolar material 1 protein) and its associated cargo to the satellites [4].
• The Bardet-Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression [4].
• Silencing of BBS4 induces PCM1 mislocalization and concomitant deanchoring of centrosomal microtubules, arrest in cell division and apoptotic cell death [4].
• In addition, we recently used positional cloning to identify the genes underlying BBS2 (ref. 16) and BBS4 (ref. 17) [5].
• Interestingly, male Bbs4-null mice do not form spermatozoa flagella, and BBS4 retinopathy involves apoptotic death of photoreceptors, the primary ciliated cells of the retina [6].

Biological context of BBS4

• We evaluated the spectrum of mutations in the recently identified BBS4 gene with a combination of haplotype analysis and mutation screening on a multiethnic cohort of 177 families [7].
• 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) [8].
• Here we report a splice variant of BBS4, which is 2556 bp in length and has an open reading frame coding a predicted 527 amino-acids protein [9].
• The phenotype in Norwegian patients with Bardet-Biedl syndrome with mutations in the BBS4 gene [2].
• The disorder showed statistically significant genetic linkage to the BBS4 locus on chromosome 15 in the affected siblings in two of the families, but the clinical features in these patients did not differ from the other cases of Bardet-Biedl syndrome [10].

Anatomical context of BBS4

• These findings correlate with the evidence that several BBS proteins, including BBS4, are expressed in the olfactory epithelium (OE) [3].

Associations of BBS4 with chemical compounds

• Intron/exon boundaries were identified, and myosin IXA DNA and RNA from BBS4 patients were evaluated for mutation [11].

Other interactions of BBS4

• BBS4 is a minor contributor to Bardet-Biedl syndrome and may also participate in triallelic inheritance [7].
• Sequence analysis of the ISLR gene in five BBS4 patients, however, showed no mutations, although a few polymorphic changes were detected [12].
• 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 [8].
• Radiation hybrid mapping demonstrates that FEM1B does not reside within the interval of chromosome 15 containing the BBS4 locus [13].

References