Tesson F, Donger C, Denjoy I, Berthet M, Bennaceur M, Petit C, Coumel P, Schwarts K, Guicheney P
INSERM UR153, Hôpital Pitié-Salpêtrière, Institut de Myologie, Paris, France.
J Mol Cell Cardiol. 1996 Sep;28(9):2051-5. doi: 10.1006/jmcc.1996.0198.
The KCNE1 gene encodes a small protein, IsK, of 14.4 kDa, with a single transmembrane domain, and is part of a potassium channel expressed in the heart. This channel is thought to underly the very slow component of the cardiac delayed rectifying current which controls the duration and the degree of ventricular repolarization. This suggested that KCNE1 could be the morbid gene responsible for an autosomal recessive cardio-auditory disease, the Jervell and Lange-Nielsen syndrome, characterized by ventricular repolarization abnormalities and recurrent syncopes leading eventually to sudden death associated with a bilateral congenital deafness. By linkage analysis in four consmanguinous families, using microsatellite markers of chromosome 21 as well as KCNE1 intragenic polymorphisms, we excluded KCNE1 as a candidate gene for Jervell and Lange-Nielsen syndrome. In addition, we described a new polymorphism, a G-to-A substitution at position 253, in the KCNE1 coding sequence detectable by SSCP analysis or RFLP.
KCNE1基因编码一种14.4 kDa的小蛋白IsK，其具有单个跨膜结构域，是心脏中表达的钾通道的一部分。该通道被认为是心脏延迟整流电流非常缓慢成分的基础，该成分控制心室复极化的持续时间和程度。这表明KCNE1可能是导致常染色体隐性心脏听觉疾病——耶尔韦尔和朗格-尼尔森综合征的致病基因，该疾病的特征是心室复极化异常和反复发作的晕厥，最终导致与双侧先天性耳聋相关的猝死。通过对四个近亲家庭进行连锁分析，使用21号染色体的微卫星标记以及KCNE1基因内多态性，我们排除了KCNE1作为耶尔韦尔和朗格-尼尔森综合征候选基因的可能性。此外，我们描述了一种新的多态性，即KCNE1编码序列中第253位的G到A替换，可通过单链构象多态性分析（SSCP）或限制性片段长度多态性（RFLP）检测到。
