Al-Aama J Y, Al-Ghamdi S, Bdier A Y, AlQarawi A, Jiman O A, Al-Aama N, Al-Aata J, Wilde A A M, Bhuiyan Z A
Department of Genetic Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia; Princess Al Jawhara Albrahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah, Saudi Arabia.
Clin Genet. 2015;87(1):74-9. doi: 10.1111/cge.12330. Epub 2013 Dec 27.
We sought to explore the genotype-phenotype of Jervell and Lange-Nielsen syndrome (JLNS) patients in Saudi Arabia. We have also assessed the plausible effect of consanguinity into the pathology of JLNS. Six families with at least one JLNS-affected member attended our clinic between 2011 and 2013. Retrospective and prospective clinical data were collected and genetic investigation was performed. Pathogenic mutations in the KCNQ1 gene were detected in all JLNS patients. The homozygous mutations detected were Leu273Phe, Asp202Asn, Ile567Thr, and c.1486_1487delCT and compound heterozygous mutations were c.820_ 830del and c.1251+1G>T. All living JLNS patients except one had a QTc of >500 ms and a history of recurrent syncope. β-Blockers abolished the cardiac-related events in all patients except two siblings with homozygous Ile567Thr mutation. Four of the six mutations were originally reported in autosomal dominant long QT syndrome (LQTS) patients. Eighty percent of the heterozygote mutation carriers showed prolongation of QTc, but majority of these reported no symptoms attributable to arrhythmias. Mutations detected in this study will be advantageous in tribe and region-specific cascade screening of LQTS in Saudi Arabia.
我们试图探究沙特阿拉伯杰韦尔和朗格 - 尼尔森综合征（JLNS）患者的基因型 - 表型。我们还评估了近亲结婚对JLNS病理的可能影响。2011年至2013年间，六个至少有一名JLNS患者的家庭前来我们诊所就诊。我们收集了回顾性和前瞻性临床数据并进行了基因检测。在所有JLNS患者中均检测到KCNQ1基因的致病突变。检测到的纯合突变有Leu273Phe、Asp202Asn、Ile567Thr和c.1486_1487delCT，复合杂合突变有c.820_830del和c.1251 + 1G>T。除一名患者外，所有存活的JLNS患者QTc均>500毫秒，并有反复晕厥史。除两名携带纯合Ile567Thr突变的兄弟姐妹外，β受体阻滞剂消除了所有患者的心脏相关事件。六个突变中有四个最初是在常染色体显性长QT综合征（LQTS）患者中报道的。80%的杂合突变携带者QTc延长，但其中大多数人没有可归因于心律失常的症状。本研究中检测到的突变将有利于沙特阿拉伯特定部落和地区的LQTS级联筛查。
