Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.
Heart Rhythm. 2011 Apr;8(4):541-7. doi: 10.1016/j.hrthm.2010.11.043. Epub 2010 Nov 30.
The Y111C/KCNQ1 mutation causes a dominant-negative effect in vitro but a benign clinical phenotype in a Swedish long QT syndrome population.
The purpose of this study was to investigate the origin (genealogic, geographic, genetic, and age) of the Y111C/KCNQ1 mutation in Sweden.
We identified 170 carriers of the Y111C/KCNQ1 mutation in 37 Swedish proband families. Genealogic investigation was performed for all families. Haplotype analysis was performed in 26 probands, 21 family members, and 84 healthy Swedish controls, using 15 satellite markers flanking the KCNQ1 gene. Mutation age was estimated using ESTIAGE and DMLE computer software and regional population demographic data.
All probands were traced back to a northern river valley region. A founder couple born in 1605/1614 connected 26 of 37 families. Haplotyped probands shared 2-14 (median 10) uncommon alleles, with frequencies ranging between 0.01 and 0.41 (median 0.16) in the controls. The age of the mutation was estimated to 24 generations (95% confidence interval 18; 34), that is, 600 years (95% confidence interval 450; 850) assuming 25 years per generation. The number of now living Swedish Y111C mutation carriers was estimated to approximately 200-400 individuals for the mutation age span 22-24 generations and population growth rates 25%-27%.
The Y111C/KCNQ1 mutation is a Swedish long QT syndrome founder mutation that was introduced in the northern population approximately 600 years ago. Enrichment of the mutation was enabled by a mild clinical phenotype and strong regional founder effects during population development of the northern inland. The Y111C/KCNQ1 founder population constitutes an important asset for future genetic and clinical studies.
Y111C/KCNQ1 突变在体外产生显性负效应，但在瑞典长 QT 综合征人群中表现为良性临床表型。
本研究旨在探讨瑞典 Y111C/KCNQ1 突变的起源（基因、地理、遗传和年龄）。
我们在 37 个瑞典先证者家族中发现了 170 名 Y111C/KCNQ1 突变携带者。对所有家族进行了系谱调查。对 26 名先证者、21 名家族成员和 84 名瑞典健康对照者进行了 KCNQ1 基因侧翼的 15 个卫星标记的单体型分析。使用 ESTIAGE 和 DMLE 计算机软件和区域人口人口统计学数据估计突变年龄。
所有先证者均追溯到一个北部河谷地区。一对生于 1605/1614 年的创始人夫妇将 37 个家族中的 26 个联系起来。单体型先证者共享 2-14 个（中位数 10）罕见等位基因，在对照组中的频率范围为 0.01 至 0.41（中位数 0.16）。突变年龄估计为 24 代（95%置信区间 18；34），即 600 年（95%置信区间 450；850），假设每代 25 年。在 22-24 代突变年龄范围内，瑞典 Y111C 突变携带者的现有人数估计约为 200-400 人，人口增长率为 25%-27%。
Y111C/KCNQ1 突变是瑞典长 QT 综合征的一个创始突变，大约在 600 年前在北方人口中引入。在北方内陆人口发展过程中，轻微的临床表型和强烈的区域创始效应促进了突变的富集。Y111C/KCNQ1 创始人群是未来遗传和临床研究的重要资产。
