Molecular genetic and genetic correlations in sodium channelopathies: lack of founder effect and evidence for a second gene.
Molecular genetic and genetic correlations in sodium channelopathies: lack of founder effect and evidence for a second gene.
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钠通道病的分子遗传和遗传相关性：缺乏奠基者效应和第二个基因的证据。
DOI：
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发表时间：
1993
影响因子：
9.8
通讯作者：
H. Wessel
中科院分区：
文献类型：
--
作者：
J. Wang;J. Zhou;S. Todorovic;W. Feero;F. Barany;R. Conwit;I. Hausmanowa;A. Fidziańska;K. Arahata;H. Wessel
我们提出了一个相关的分子遗传数据（突变）和遗传数据（二核苷酸重复多态性）的队列7高钾型周期性麻痹（HyperPP）和两个先天性副肌强直（PC）的家庭来自不同的种族背景。我们发现，成人骨骼肌钠通道基因的三个先前确定的点突变发生在两个不同的二核苷酸重复单倍型。这些结果表明，二核苷酸重复单倍型不能预测等位基因异质性钠通道病，与以前的建议。此外，我们确定了一个HyperPP家系，其中显性疾病与钠通道基因无关。因此，第二个基因座可以产生相似的临床表型。这个家系中的一些个体表现出碱基变化，导致进化上保守的氨基酸的非保守取代。因为这种变化不存在于240个正常染色体中，并且接近另一个HyperPP突变，所以满足了最常用的突变而不是多态性的标准。然而，连锁研究使用单链构象多态性衍生和序列衍生的单倍型排除了这种碱基变化作为一个致病突变：这些数据作为一个警示的例子，潜在的陷阱，在描绘的功能改变点突变。
We present a correlation of molecular genetic data (mutations) and genetic data (dinucleotide-repeat polymorphisms) for a cohort of seven hyperkalemic periodic paralysis (HyperPP) and two paramyotonia congenita (PC) families from diverse ethnic backgrounds. We found that each of three previously identified point mutations of the adult skeletal muscle sodium-channel gene occurred on two different dinucleotide-repeat haplotypes. These results indicate that dinucleotide-repeat haplotypes are not predictive of allelic heterogeneity in sodium channelopathies, contrary to previous suggestions. In addition, we identified a HyperPP pedigree in which the dominant disorder was not linked to the sodium-channel gene. Thus, a second locus can give rise to a similar clinical phenotype. Some individuals in this pedigree exhibited a base change causing the nonconservative substitution of an evolutionarily conserved amino acid. Because this change was not present in 240 normal chromosomes and was near another HyperPP mutation, is fulfilled the most commonly used criteria for being a mutation rather than a polymorphism. However, linkage studies using single-strand conformation polymorphism-derived and sequence-derived haplotypes excluded this base change as a causative mutation: these data serve as a cautionary example of potential pitfalls in the delineation of change-of-function point mutations.
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SCN4A 基因座的二核苷酸重复多态性表明高钾性周期性麻痹和先天性副肌强直的等位基因异质性。
影响因子：
9.8
作者：
McClatchey,AI;Trofatter,J;McKenna-Yasek,D;Raskind,W;Bird,T;Pericak-Vance,M;Gilchrist,J;Arahata,K;Radosavljevic,D;Worthen,HG
通讯作者：
Worthen,HG
对大型高钾性周期性麻痹谱系的分析支持与钠通道基因座的紧密联系。
影响因子：
9.8
作者：
Ptacek,LJ;Tyler,F;Trimmer,JS;Agnew,WS;Leppert,M
通讯作者：
Leppert,M
先天性副肌强直和高钾性周期性麻痹映射到相同的钠通道基因位点。
影响因子：
9.8
作者：
Ptacek,LJ;Trimmer,JS;Agnew,WS;Roberts,JW;Petajan,JH;Leppert,M
通讯作者：
Leppert,M
囊性纤维化跨膜电导调节因子 (CFTR) 基因的内含子 17b 中存在一簇高度多态性二核苷酸重复序列。
影响因子：
9.8
作者：
Zielenski,J;Markiewicz,D;Rininsland,F;Rommens,J;Tsui,LC
通讯作者：
Tsui,LC