Ann Lab Med.  2014 Sep;34(5):395-398. 10.3343/alm.2014.34.5.395.

Large Deletion in KCNQ1 Identified in a Family with Jervell and Lange-Nielsen Syndrome

• Sung JY
• Bae EJ
• Park S
• Kim SY
• Hyun YJ
• Park SS
• Seong MW

• KMID: 1791957
• DOI: http://doi.org/10.3343/alm.2014.34.5.395

Abstract

Long QT syndrome (LQTS) is a genetically heterogeneous disorder associated with sequence variations in more than 10 genes; in some cases, it is caused by large deletions or duplications among the main, known LQTS-associated genes. Here, we describe a 14-month-old Korean boy with congenital hearing loss and prolonged QT interval whose condition was clinically diagnosed as Jervell and Lange-Nielsen syndrome (JLNS), a recessive form of LQTS. Genetic analyses using sequence analysis and multiplex ligation-dependent probe amplification (MLPA) assay revealed a large deletion spanning exons 7-10 as well as a frameshift mutation (c.1893dup; p.Arg632Glnfs*20). To our knowledge, this is the first report of a large deletion in KCNQ1 identified in JLNS patients. This case indicates that a method such as MLPA, which can identify large deletions or duplications needs to be considered in addition to sequence analysis to diagnose JLNS.

Keyword

Jervell and Lange-Nielsen syndrome; KCNQ1 mutation; Multiplex ligation-dependent probe amplification; Exon deletion

MeSH Terms

Adolescent
Alleles
Base Sequence
Electrocardiography
Exons
Frameshift Mutation
Heterozygote
Humans
Jervell-Lange Nielsen Syndrome/diagnosis/*genetics
KCNQ1 Potassium Channel/*genetics
Male
Nucleic Acid Amplification Techniques
Pedigree
Sequence Analysis, DNA
Sequence Deletion
KCNQ1 Potassium Channel

Figure

• 

  Fig. 1 Family pedigree. The older brother with a history of syncope and long QTc carries the same mutations as the proband (marked with arrow), i.e., large exon deletion and frameshift sequence mutation. Each mutation was inherited from one of the parents; the exon deletion from the father and the frameshift mutation from the mother.

• 

  Fig. 2 (A) Sequencing analysis revealed a frameshift mutation (c.1893dup; p.Arg632Glnfs*20) in the proband, his mother, and his brother. (B) On the basis of the result of multiplex ligation-dependent probe amplification, 4 exons (exons 9, 10, 7, and 8 in this order) with half the copy number were identified, indicating a large deletion in the proband, his father, and his brother.

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