Larsen L A, Fosdal I, Andersen P S, Kanters J K, Vuust J, Wettrell G, Christiansen M
Department of Clinical Biochemistry, Statens Serum Institut, Copenhagen, Denmark.
Eur J Hum Genet. 1999 Sep;7(6):724-8. doi: 10.1038/sj.ejhg.5200323.
We describe a Swedish family with the proband and his brother suffering from severe Romano-Ward syndome (RWS) associated with compound heterozygosity for two mutations in the KVLQT1 (also known as KCNQ1 and KCNA9) gene (R518X and A525T). The mutations were found to segregate as heterozygotes in the maternal and the paternal lineage, respectively. None of the heterozygotes exhibited clinical long QT syndrome (LQTS). No hearing defects were found in the proband. The data strongly indicates that the compound heterozygosity for R518X and A525T is the cause of an autosomal recessive form of RWS in this family. Our findings support the implication of a higher frequency of gene carriers than previously expected. We suggest that relatives of 'sporadic RWS' patients should be considered potential carriers, at risk of dying suddenly from drug-induced LQTS.
我们描述了一个瑞典家庭，先证者及其兄弟患有严重的罗曼诺-沃德综合征（RWS），与KVLQT1（也称为KCNQ1和KCNA9）基因中的两个突变（R518X和A525T）的复合杂合性相关。发现这些突变分别作为杂合子在母系和父系谱系中分离。没有杂合子表现出临床长QT综合征（LQTS）。在先证者中未发现听力缺陷。数据强烈表明，R518X和A525T的复合杂合性是该家族中常染色体隐性形式RWS的病因。我们的发现支持了基因携带者频率高于先前预期的观点。我们建议，“散发性RWS”患者的亲属应被视为潜在携带者，有因药物诱导的LQTS而突然死亡的风险。
