The congenital myasthenic syndrome mutation RAPSN N88K derives from an ancient Indo-European founder

Congenital Myasthenic Syndromes - Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction

“…N88K in RAPSN is one of the most frequently observed mutations in CMS (Muller et al, 2003;Richard et al, 2003). We reported lack of a founder haplotype for N88K , but analysis of markers closer to RAPSN later revealed possible presence of a shared haplotype (Muller et al, 2004) suggesting that N88K is an ancient founder mutation but subsequent multiple recombination events and divergence of microsatellite markers have narrowed the shared haplotype region. Functional analysis L14P, N88K, and 553ins5 disclosed that these mutations have no effect on self-association of rapsyn but impair colocalization of rapsyn with AChR .…”

Congenital myasthenic syndromes: Achievements and limitations of phenotype-guided gene-after-gene sequencing in diagnostic practice: A study of 680 patients

“…3). The known common founder mutation RAPSN p.Asn88Lys [Muller et al, 2004a] contributed significantly to the overall frequency of RAPSN defects as it has been found in 39 patients and therefore more than 90% of RAPSN ‐positive patients on at least one allele (Supp. Table S2g).…”

Investigation for RAPSN and DOK‐7 mutations in a cohort of seronegative myasthenia gravis patients

“…Comparing allele frequencies in the SNPs (Table 2), we found no differences in allelic distribution between SNMG patients and controls ( P = 0.12). The four chromosomes containing N88K all had a C at position c.456, which is part of a common conserved haplotype in N88K alleles 18…”