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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 - Ann Lab Med (2014)

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

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.

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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.
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Figure 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.

Mentions: Genetic analysis revealed compound heterozygous mutations in KCNQ1 consisting of a large deletion (exons 7-10, c.922-?_c.1393+?del, reference sequence: NM_000218.2) and a frameshift mutation (c.1893dup; p.Arg632Glnfs*20) in the proband and his brother. The proband's father was heterozygous for the large deletion (exons 7-10) but did not carry the frameshift mutation, whereas the proband's mother was heterozygous for the frameshift mutation (c.1893dup; p.Arg632Glnfs*20) but neither exon deletions nor duplications were detected (Fig. 1 and 2).


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 - Ann Lab Med (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151011&req=5

Figure 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.
Mentions: Genetic analysis revealed compound heterozygous mutations in KCNQ1 consisting of a large deletion (exons 7-10, c.922-?_c.1393+?del, reference sequence: NM_000218.2) and a frameshift mutation (c.1893dup; p.Arg632Glnfs*20) in the proband and his brother. The proband's father was heterozygous for the large deletion (exons 7-10) but did not carry the frameshift mutation, whereas the proband's mother was heterozygous for the frameshift mutation (c.1893dup; p.Arg632Glnfs*20) but neither exon deletions nor duplications were detected (Fig. 1 and 2).

Bottom Line: 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).

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

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.

Show MeSH
Related in: MedlinePlus