Disease relevance of RAPSN

• We here report two novel E-box mutations in the RAPSN promoter region in eight congenital myasthenic syndrome patients [1].

High impact information on RAPSN

• Impaired transcriptional activities of the RAPSN promoter region predict reduced rapsyn expression and endplate acetylcholine receptor deficiency [1].
• RAPSN encodes rapsyn, a 43 kDa postsynaptic peripheral membrane protein that clusters the nicotinic acetylcholine receptor at the motor endplate [1].
• Analysis of PCR amplifications, first from somatic cell hybrids and subsequently from radiation hybrids, localizes the human RAPSN gene locus to chromosome 11p11.2-p11.1 in close proximity to ACP2 [2].
• Cloning of cDNA encoding human rapsyn and mapping of the RAPSN gene locus to chromosome 11p11.2-p11.1 [2].
• In most patients, RAPSN N88K was identified, either homozygously or heteroallelic to a second missense mutation [3].

Chemical compound and disease context of RAPSN

• Novel truncating RAPSN mutations causing congenital myasthenic syndrome responsive to 3,4-diaminopyridine [4].

Biological context of RAPSN

• A sporadic CMS patient from Germany was analyzed for RAPSN mutations by RFLP, long-range PCR and sequence analysis [3].
• We hypothesize that numerous interspersed Alu elements may predispose the RAPSN locus for genetic rearrangements [3].
• Surprisingly, two N88K homozygous patients had one asymptomatic relative each who carried the same genotype, suggesting that additional genetic factors to RAPSN mutations are required for disease expression [5].
• RESULTS: For the putative splice mutation (IVS1-15C>A), the authors constructed wild-type and mutated RAPSN minigenes for transfection and subsequent RNA analysis [6].
• METHODS: The authors analyzed the RAPSN gene for sequence variations and carried out in vitro studies in order to delineate the potential pathogenicity of the three novel RAPSN mutations [6].

Anatomical context of RAPSN

• Here we expressed RAPSN mutations A25V, N88K, R91L, L361R and K373del in TE671 cells and in rapsyn-/- myotubes to determine their pathogenic mechanisms [7].

Associations of RAPSN with chemical compounds

• These studies illustrate how masses can be determined for nAChR subunits and for other protein components in Torpedo membrane preparations, such as RAPsyn and Na(+)-K(+)-ATPase alpha and beta subunits [8].

References