Disease relevance of CHRNB2

• Twenty-four autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) probands were analyzed for the presence of V287L and V287M mutations in the CHRNB2 gene, which have been recently associated with the disease [1].

Psychiatry related information on CHRNB2

• Candidate gene association studies of the alpha 4 (CHRNA4) and beta 2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease [2].
• The CHRNB2 mutation I312M is associated with epilepsy and distinct memory deficits [3].

High impact information on CHRNB2

• Compared with the CHRNA4 and CHRNB2 mutations reported elsewhere, CHRNA2 mutations cause a more complex and finalized ictal behavior [4].
• CHRNB2 is a new gene for idiopathic epilepsy, the second acetylcholine receptor subunit implicated in ADNFLE [5].
• CHRNB2 is the second acetylcholine receptor subunit associated with autosomal dominant nocturnal frontal lobe epilepsy [5].
• A similar analysis for the four SNPs within CHRNB2 did not reveal significant association with the three ND measures [6].
• Employing logistic regression and controlling for known risk factors, the best-fitting model for smoking initiation encompassed a 5 SNP haplotype in CHRNB2, neuroticism and novelty seeking (P=5.9 x 10(-14), Nagelkerke r(2)=0.30) [7].

Biological context of CHRNB2

• Here we provide the information on the genomic structures of both the CHRNB2 and the CHRNA3 genes that is necessary for comprehensive mutational analyses, and we refine the genomic assignment of CHRNB2 on chromosome 1 [8].
• Exon 5 of CHRNA4 and CHRNB2 genes, harboring all the known mutations, was sequenced in the probands [9].
• Two novel missense point mutations, Ser413Leu in the CHRNA4 gene and Gln397Pro in the CHRNB2 gene, were identified in two different AD cases but were not found in other AD cases and controls [10].
• We studied six single-nucleotide polymorphisms (SNPs) in the CHRNA4 gene and four SNPs in the CHRNB2 gene with respect to nicotine dependence in a collection of 901 subjects (815 siblings and 86 parents) from 222 nuclear families with multiple nicotine-addicted siblings [11].

Anatomical context of CHRNB2

• To identify the possible mutations and/or polymorphisms of neuronal nicotinic acetylcholine receptor (nAChR) genes related to the pathogenesis of sporadic AD, we have performed mutational analyses of the major neuronal nAChR genes (CHRNA3, 4, 7 and CHRNB2) expressed in central nervous system [10].

Other interactions of CHRNB2

• But despite some positive linkage results including the CHRNA3-CHRNA5-CHRNB2 cluster on chromosome 15q24, no further mutations have been found so far [12].
• Alpha4-subunits often assemble together with beta2-subunits (gene symbol CHRNB2) to build heteromeric nAChRs [8].
• Individual gene analysis suggests that CHRNA2 and CHRNB2 may play a particular role in this involvement [13].
• Mutational screening was performed by sequencing a polymerase chain reaction-amplified CHRNB2 DNA fragment, spanning the whole exon 5, which contains the V287L and V287M mutations and codes for approximately 65% of the mature protein [1].

Analytical, diagnostic and therapeutic context of CHRNB2

• A search for mutations of the genes coding for the most widely distributed nicotinic receptor subtype alpha4beta2 (CHRNA4/CHRNB2) has been performed in AD patients by screening the coding regions of both genes by single strand conformation analysis and heteroduplex analysis of fibroblast-derived genomic DNA [14].

References