Common founder effect of rapsyn N88K studied using intragenic markers

Journal of Human Genetics
Vanessa Dunne, R Maselli

Abstract

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.

References

May 13, 1999·Brain Research. Developmental Brain Research·M GautamJ R Sanes
Jan 16, 2002·American Journal of Human Genetics·Kinji OhnoMargherita Milone
Mar 26, 2003·Human Molecular Genetics·Kinji OhnoAndrew G Engel
May 3, 2003·Nature Reviews. Neuroscience·Andrew G EngelSteven M Sine
May 6, 2003·Journal of Human Genetics·Vanessa Dunne, Ricardo A Maselli
Aug 21, 2003·Muscle & Nerve·Ricardo A MaselliRobert L Wollmann

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Citations

Aug 10, 2007·Expert Reviews in Molecular Medicine·Juliane S MüllerHanns Lochmüller

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