Meyer-Kleine C, Otto M, Zoll B, Koch M C
Medizinisches Zentrum für Humangenetik, Philipps-Universität Marburg, Germany.
Hum Genet. 1994 Jun;93(6):707-10. doi: 10.1007/BF00201577.
Eighteen German families with a history of paramyotonia congenita (PC) were characterised by genetic and mutational analysis at the SCN4A locus, which encodes the alpha-subunit of the adult skeletal muscle sodium channel. We concentrated our analysis primarily on these families to test the hypothesis that a predominance of one common mutation occurs in all German PC families and that this mutation arose in a common ancestor originating in the North-West of the country. The present eighteen PC families exhibit two different mutations (R1448C and R1448H) on various SCN4A dinucleotide repeat haplotypes and therefore the majority of the mutations probably occurred independently. However, the R1448H mutation is extremely frequent in the North-West of Germany (Ravensberger Land) on a specific SCN4A microsatellite haplotype, indicating a founder effect within this subpopulation. Our results suggest that the R1448C/R1448H mutations are by far the most common to be associated with the PC phenotype in the German population.
对18个有先天性副肌强直（PC）病史的德国家庭进行了基因和突变分析，分析对象为编码成人骨骼肌钠通道α亚基的SCN4A基因座。我们主要集中分析这些家庭，以检验以下假设：在所有德国家庭中，一种常见突变占主导地位，且该突变起源于德国西北部的一个共同祖先。目前这18个PC家庭在各种SCN4A二核苷酸重复单倍型上表现出两种不同的突变（R1448C和R1448H），因此大多数突变可能是独立发生的。然而，R1448H突变在德国西北部（拉文斯贝格地区）的一种特定SCN4A微卫星单倍型上极为常见，表明该亚群内存在奠基者效应。我们的结果表明，R1448C/R1448H突变是德国人群中与PC表型相关的最常见突变。
