Genotype-phenotype analysis of three Chinese families with Jervell and Lange-Nielsen syndrome

• Published in: Journal of cardiovascular disease research Vol. 3; no. 2; pp. 67 - 75
• Main Authors: Gao, Yuanfeng, Li, Cuilan, Liu, Wenling, Qiu, Xiaoliang, Liang, Ruijuan, Li, Lei, Hu, Dayi, Wu, Robby, Zhang, Li
• Format: Journal Article
• Language: English
• Published: India Elsevier B.V 01.04.2012; Medknow Publications and Media Pvt. Ltd; Elsevier Limited; Medknow Publications & Media Pvt Ltd
• Subjects: Cardiovascular disease; Care and treatment; Case studies; Chinese; Compound heterozygous mutation; Deafness; Diagnosis; Family; frameshift mutation; Genetic testing; Genetics; Genotype; Genotype & phenotype; Health aspects; Identification and classification; Jervell and Lange-Nielsen syndrome; KCNE1; KCNQ1; long QT syndrome; Mutation; Original; Phenotype; Romano-Ward syndrome; single nucleotide polymorphism; China; KCNE1; long QT syndrome; Romano-Ward syndrome; single nucleotide polymorphism; KCNQ1; Compound heterozygous mutation; frameshift mutation; Jervell and Lange-Nielsen syndrome
• ISSN: 0975-3583; 0976-2833
• DOI: 10.4103/0975-3583.95357

Background: Long QT syndrome (LQTS) is characterized by QT prolongation, syncope and sudden death. This study aims to explore the causes, clinical manifestations and therapeutic outcomes of Jervell and Lange-Nielsen syndrome (JLNS), a rare form of LQTS with congenital sensorineural deafness, in Chinese individuals. Materials and Methods: Three JLNS kindreds from the Chinese National LQTS Registry were investigated. Mutational screening of KCNQ1 and KCNE1 genes was performed by polymerase chain reaction and direct DNA sequence analysis. LQTS phenotype and therapeutic outcomes were evaluated for all probands and family members. Results: We identified 7 KCNQ1 mutations. c.l032_1117dup (p.Ser373TrpfsX10) and c,1319delT (p.Val440AlafsX26) were novel, causing JLNS in a 16-year-old boy with a QTc (QT interval corrected for heart rate) of 620 ms and recurrent syncope. c.605-2A>Gandc.815G>A(p.Gly272Asp) caused JLNS ina 12-year-oldgirlandher5-year-old brother, showing QTc of 590 to 600 ms and recurrent syncope. The fourth JLNS case, a 46-year-old man carrying c.1032G>A (p.Ala344Alasp) and c.569G>A (p.Argl90Gln) and with QTc of460 ms, has been syncope-free since âge 30. His 16-year-old daughter carries novel missense mutation c.574C>T (p.Aigl92Cys) and c.l032G>A(p. Ala344Alasp) and displayed a severe phenotype of Romano-Ward syndrome (RWS) characterized by a QTc of 530 ms and recurrent syncope with normal hearing. Both the father and daughter also carried c.253G>A (p.Asp85Asn; rsl805128), a rare single nucleotide polymorphism (SNP) on KCNE1. Bizarre T waves were seen in 3/4 JLNS patients. Symptoms were improved and T wave abnormalities became less abnormal after appropriate treatment. Conclusion: This study broadens the mutation and phenotype spectrums of JLNS. Compound heterozygous KCNQ1 mutations can result in both JLNS and severe forms of RWS in Chinese individuals.