Possible founder effect of rapsyn N88K mutation and identification of novel rapsyn mutations in congenital myasthenic syndromes

Richard, Pascale; Gaudon, Karen; Andreux, F.; Yasaki, E; Prioleau, Cassandra; Bauché, Stéphanie; Barois, A; Ioos, Christine; Mayer, M.; Routon, M. C.; Mokhtari, M Sataei; Leroy, Jean‐Paul; Fournier, Emmanuel; Hainque, Bernard; Koenig, Jeanine; Fardeau, Michel; Eymard, B.; Hantaı̈, Daniel

doi:10.1136/jmg.40.6.e81

Cited by 51 publications

(42 citation statements)

References 13 publications

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“…Since then, we and others (Muller et al 2003;Richard et al 2003) have confirmed this initial observation with further reports of CMS patients due to mutations in RAPSN. Of note, all patients reported to date carry the N88K allele, either homozygous or heteroallelic, with a second mutation, with the exception of those with mutations in the RAPSN promoter region .…”

Section: Introductionsupporting

confidence: 78%

Common founder effect of rapsyn N88K studied using intragenic markers

Dunne

Maselli

2004

J Hum Genet

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Mutations in the human gene encoding rapsyn have been linked to a recessive form of postsynaptic congenital myasthenic syndrome due to deficient clustering of acetylcholine receptors at the endplate. All patients reported to date carry the N88K mutation, suggesting a possible common founder effect. To decrease the likelihood of a recombination event occurring within the span of neighboring microsatellite markers, we used seven intragenic single nucleotide polymorphisms (SNPs) spanning 8 kb to characterize the haplotype associated with N88K. In three affected N88K homozygous individuals, we identified a common haplotype present in all heterozygous carriers of N88K. Of note, in two asymptomatic N88K homozygous individuals, a second haplotype was present that differed at three SNP sites downstream from the N88K mutation. Our findings of a common haplotype associated with the N88K mutation support a founder effect. The discordant haplotype found in homozygous individuals suggests that recombination events may have occurred within the rapsyn gene and that this may have implications in the phenotypic expression of the disease.

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Section: Introductionsupporting

confidence: 78%

Common founder effect of rapsyn N88K studied using intragenic markers

Dunne

Maselli

2004

J Hum Genet

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“…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.…”

Section: Endplate Achr Deficiency Due To Defects In Rapsynmentioning

confidence: 68%

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

Ohno¹,

Ito²,

Engel³

2012

Neuromuscular Disorders

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“…N88K occurred with high frequency, as observed in other series. 9,18,26,32 Six mutations reported here are novel and family analysis indicates they are recessive.…”

Section: -21mentioning

confidence: 75%

“…9,10,16,18,[25][26][27][28][29][30][31] The mutations are dispersed through the entire RAPSN gene. N88K occurred with high frequency, as observed in other series.…”

Section: -21mentioning

confidence: 99%