Multiexon deletions account for 15% of Congenital Myasthenic Syndrome with RAPSN mutations after negative DNA Sequencing
Résumé
Introduction: Post-synaptic congenital myasthenic syndromes (CMSs) (OMIM_ #608931) is a group of genetic disorders affecting neuromuscular transmission and due to acetylcholine receptor (AChR) deficiency in 80% of cases.[1] These autosomal recessive CMSs may be caused by mutations in genes encoding the AChR or one of the AChR-clustering or anchoring proteins, rapsyn, Dok-7 or MuSK.[1-4] Spectra of rapsyn mutations show allelic heterogeneity and suggest that the common substitution p.Asn88Lys (N88K) (variant_021217 in Q13702) results in less stable AChR clusters.[5] Until recently, all patients harbouring mutations in RAPSN are either homozygous for the p.Asn88Lys substitution or heteroallelic for p.Asn88Lys and a mutation which is in most of cases an amino acid substitution but can be also a null allele.[6] Analysis of disease severity in patients suggested that the second mutant allele may largely determine severity of the phenotype.[7] Recently, a patient with two non p.Asn88Lys in RAPSN has been described and the first chromosomal deletion event was described by Müller and colleagues.[8,9]
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