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Mutations in RAPSN, a gene encoding rapsyn, a molecule that clusters acetylcholine receptors at the motor endplate,1 cause endplate acetylcholine receptor deficiency.2–7
Müller and colleagues recently reported that N88K is a frequent mutation in RAPSN.5 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.
Haplotype analysis. (A) Physical map of microsatellite markers (open circles) flanking RAPSN (closed circle) according to the NCBI uniSTS database and Map Viewer Build 33. Positions of markers are slightly different from those reported by us3 and by Müller et al,5 because the Human Genome Project has recently been completed for this region (GenBank accession number NT_009237). Numbers in parentheses indicate genetic distances from RAPSN in centiMorgans according to the deCODE recombination map.9 The genetic distances are approximate, because RAPSN has not been positioned in any recombination map. na, Not available. p values represent Fisher’s two tailed exact test to see if a dominant genotype at each marker is linked to N88K. (B) Identified haplotypes. F1–F10 denote families 1 to 10. K and N in the haplotype names represent mutant K88 and wild type N88, respectively. Genotypes dominant in the mutant K88 chromosomes are shaded. Numbers in haplotypes represent the size of PCR product. na, Not available, because all family members were heterozygous for two morphs. In F8, all members carried morphs 260 and 264 at D11S4117. In F10, all members carried morphs 277 and 283 at D11S4174.
Richard and colleagues also recently reported that N88K arises from a common founder; they …