ONLINE MUTATION REPORT Lack of founder haplotype for the rapsyn N88K mutation: N88K is an ancient founder mutation or arises from multiple founders

M utations in RAPSN, a gene encoding rapsyn, a molecule that clusters acetylcholine receptors at the motor endplate, cause endplate acetylcholine receptor deficiency. Müller and colleagues recently reported that N88K is a frequent mutation in RAPSN. By genotyping 17 mutant K88 chromosomes for two RAPSN polymorphisms (IVS3-11delC and 456T/C) and a microsatellite marker D11S4117 (fig 1A) in 12 patients from 10 independent central or western European families, they found that 14 of 17 mutant chromosomes shared a common haplotype and concluded that N88K arises from a common founder. Richard and colleagues also recently reported that N88K arises from a common founder; they genotyped 10 mutant K88 chromosomes in five patients from four families and from five healthy controls heterozygous for N88K. They showed that 9/10 mutant chromosomes shared a common haplotype for D11S1252, D11S4109, and D11S4117 (fig 1A). Both groups also demonstrated that a distant microsatellite marker, D11S986, was not linked to N88K. 6 We also searched for a founder effect for N88K in our cohort of patients using six microsatellite markers and five RAPSN polymorphisms, and found that there is no founder haplotype for N88K.