KCNQ1 mutations associated with Jervell and Lange-Nielsen syndrome and autosomal recessive Romano-Ward syndrome in India—expanding the spectrum of long QT syndrome type 1

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• 作者：Bijal Vyas ; Ratna D. Puri ; Narayanan Namboodiri ; Mohan Nair ; Deepak Sharma ; Sireesha Movva ; Renu Saxena ; Shomu Bohora ; Neeraj Aggarwal ; Amit Vora ; Jatinder Kumar ; Tarandeep Singh and Ishwar C. Verma
• 刊名：American Journal of Medical Genetics Part A
• 出版年：2016
• 出版时间：June 2016
• 年：2016
• 卷：170
• 期：6
• 页码：1510-1519
• 全文大小：1989K
• ISSN：1552-4833

文摘

Long QT syndrome type 1 (LQT1) is the most common type of all Long QT syndromes (LQTS) and occurs due to mutations in KCNQ1. Biallelic mutations with deafness is called Jervell and Lange–Nielsen syndrome (JLNS) and without deafness is autosomal recessive Romano–Ward syndrome (AR RWS). In this prospective study, we report biallelic mutations in KCNQ1 in Indian patients with LQT1 syndrome. Forty patients with a clinical diagnosis of LQT1 syndrome were referred for molecular testing. Of these, 18 were excluded from the analysis as they did not fulfill the inclusion criteria of broad T wave ECG pattern of the study. Direct sequencing of KCNQ1 was performed in 22 unrelated probands, parents and at-risk family members. Mutations were identified in 17 patients, of which seven had heterozygous mutations and were excluded in this analysis. Biallelic mutations were identified in 10 patients. Five of 10 patients did not have deafness and were categorized as AR RWS, the rest being JLNS. Eight mutations identified in this study have not been reported in the literature and predicted to be pathogenic by in silico analysis. We hypothesize that the homozygous biallelic mutations identified in 67% of families was due to endogamous marriages in the absence of consanguinity. This study presents biallelic gene mutations in KCNQ1 in Asian Indian patients with AR JLNS and RWS. It adds to the scant worldwide literature of mutation studies in AR RWS.