Genotype-phenotype analysis of three Chinese families with Jervell and Lange-Nielsen syndrome
Keywords:
Compound heterozygous mutation, frameshift mutation, Jervell and Lange-Nielsen syndrome, KCNQ1, KCNE1, long QT syndrome, Romano-Ward syndrome, single nucleotide polymorphismAbstract
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: :HLGHQWL¿HGKCNQ1PXWDWLRQVFBGXS S6HU7USIV; DQGFGHO7 S9DO$ODIV; ZHUHQRYHOFDXVLQJ-/16LQD\HDUROGER\ZLWKD47F 47LQWHUYDOFRUUHFWHGIRUKHDUWUDWH RIPVDQG UHFXUUHQWV\QFRSHF$!*DQGF*!$ S*O\$VS FDXVHG-/16LQD\HDUROGJLUODQGKHU\HDUROG
EURWKHUVKRZLQJ47FRIWRPVDQGUHFXUUHQWV\QFRSH7KHIRXUWK-/16FDVHD\HDUROGPDQFDUU\LQJ
F*!$ S$OD$ODVS DQGF*!$ S$UJ*OQ DQGZLWK47FRIPVKDVEHHQV\QFRSHIUHHVLQFH
DJH+LV\HDUROGGDXJKWHUFDUULHVQRYHOPLVVHQVHPXWDWLRQF&!7 S$UJ&\V DQGF*!$ S
$OD$ODVS DQGGLVSOD\HGDVHYHUHSKHQRW\SHRI5RPDQR:DUGV\QGURPH 5:6 FKDUDFWHUL]HGE\D47FRI
PVDQGUHFXUUHQWV\QFRSHZLWKQRUPDOKHDULQJ%RWKWKHIDWKHUDQGGDXJKWHUDOVRFDUULHGF*!$ S$VS$VQ
UV DUDUHVLQJOHQXFOHRWLGHSRO\PRUSKLVP 613 RQKCNE1%L]DUUH7ZDYHVZHUHVHHQLQ-/16 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.
