J Korean Med Sci.  2010 Oct;25(10):1522-1525. 10.3346/jkms.2010.25.10.1522.

Jervell and Lange-Nielsen Syndrome: Novel Compound Heterozygous Mutations in the KCNQ1 in a Korean Family

• Baek JS
• Bae EJ
• Lee SY
• Park SS
• Kim SY
• Jung KN
• Noh CI

• KMID: 2157860
• DOI: http://doi.org/10.3346/jkms.2010.25.10.1522

Abstract

The Jervell and Lange-Nielsen syndrome (JLNS) is an autosomal recessive syndrome characterized by congenital deafness and cardiac phenotype (QT prolongation, ventricular arrhythmias, and sudden death). JLNS has been shown to occur due to homozygous mutation in KCNQ1 or KCNE1. There have been a few clinical case reports on JLNS in Korea; however, these were not confirmed by a genetic study. We identified compound heterozygous mutations in KCNQ1 in a 5-yr-old child with JLNS, who visited the hospital due to recurrent syncope and seizures and had congenital sensorineural deafness. His electrocardiogram revealed a markedly prolonged corrected QT interval with T wave alternans. The sequence analysis of the proband revealed the presence of novel compound heterozygous deletion/splicing error mutations (c.828-830 delCTC, p.S277del/c.921G>A, p.V307V). Each mutation in KCNQ1 was identified on the maternal and paternal side. With beta-blocker therapy the patient has remained symptom-free for three and a half years.

Keyword

Congenital Long QT Syndrome; Deafness; Mutation

MeSH Terms

Asian Continental Ancestry Group/*genetics
Child, Preschool
Electrocardiography
Exons
Family
Gene Deletion
Heterozygote
Humans
Jervell-Lange Nielsen Syndrome/diagnosis/*genetics
KCNQ1 Potassium Channel/*genetics
Male
Mutation
Pedigree
Republic of Korea

Figure

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  Fig. 1 Baseline ECG. It reveals a markedly prolonged corrected QT interval (QTc).

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  Fig. 2 Tredmill test shows a marked QTc prolongation and T wave alternas as the test progresses.

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  Fig. 3 A gene study shows that he has compound heterozygous mutations in the KCNQ1 gene: Genomic DNA sequencing shows (A) c.828_830delCTC, p.S277del, heterozygote, and (B) c.921G>A, p.V307V, heterozygote. (C) The RT-PCR detects abnormally spliced mRNA product in which the exon 6 had been skipped, (D) and sequencing of RT-PCR products confirms exon 6 skipping due to the mutation, c.921G>A, p.V307V. M, Molecular marker, NC, normal control.

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  Fig. 4 The pedigree of presented family.

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