Limits...
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.

Show MeSH

Related in: MedlinePlus

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

License
getmorefigures.php?uid=PMC4151011&req=5

Figure 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.

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)

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

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

Figure 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.
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