Identification and characterization of a novel recessive KCNQ1 mutation associated with Romano-Ward Long-QT syndrome in two Iranian families

• Published in: Journal of electrocardiology Vol. 50; no. 6; pp. 912 - 918
• Main Authors: Zafari, Zahra, Dalili, Mohammad, Zeinali, Sirus, Saber, Siamak, Fazeli Far, Amir Farjam, Akbari, Mohammad Taghi
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2017; Elsevier Science Ltd
• Subjects: Arrhythmia; Cardiac arrhythmia; Child; Electrocardiography; Female; Founder mutation; Genetic Testing; Humans; Iran; KCNQ1 Potassium Channel - genetics; LQTS; Male; Mutation; Mutation - genetics; Next generation sequencing; Pedigree; Romano-Ward Syndrome - genetics; Sequence Analysis, DNA; Iran; Founder mutation; Genetic testing; Arrhythmia; Iran; Next generation sequencing; LQTS
• ISSN: 0022-0736; 1532-8430
• DOI: 10.1016/j.jelectrocard.2017.07.012

One of the foremost causes of sudden cardiac death in the young is an inherent cardiac arrhythmia known as Long-QT syndrome (LQTS). Whereas heterozygous mutations typically lead to the Romano-Ward type of LQTS, We have provided a further evidence for the recessive transmission of a novel KCNQ1 gene mutation in two consanguineous families for the first time in Iran. Next generation sequencing, DNA Sanger sequencing and haplotype analysis were performed for genotype determination. Twelve different in silico tools were used for predicting the variant pathogenecity along with the family and population study. A novel recessive KCNQ1 variant (p.D564G) was revealed in none of the unrelated healthy individuals but four patients in two apparently unrelated families. The variant was classified as a likely pathogenic mutation by combining the resulted criteria for the changed amino acid. Identification of the novel mutation not only supports the genetic testing as a definitive diagnostic tool for detection of at risk family members, but also emphasizes its screening in Iranian LQTS patients as this mutation is very likely a founder mutation in Iran. •Detection of a novel recessive KCNQ1 mutation in two Iranian families with Autosomal dominant type of LQTS.•Classifying the mutation as a likely pathogenic mutation.•Detection of the mutation as a founder mutation.•Detection of the mutation in none of the unrelated healthy individuals.•The necessity of the genetic testing for detection of at risk family members.