A Candidate Locus Approach Identifies a Long QT Syndrome Gene Mutation

Beery, Theresa A.; Dyment, Macaira; Shooner, Kerry; Knilans, Timothy K.; Benson, D. Woodrow

doi:10.1177/1099800403257281

Cited by 5 publications

(1 citation statement)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The glycine at position 168 of the KCNQ1 protein is part of the second transmembrane domain of the ion channel, a critical region for channel function. This mutation had been reported previously in at least ten families [Donger et al, 1997; Splawski et al, 1998, 2000; Beery et al, 2003; Westenskow et al, 2005; Márquez et al, 2006], including one in which it was homozygous, causing Jervill Lange‐Nielsen syndrome [Márquez et al, 2006]. As shown by boxes in Figure 1 and in Table I, we sequenced this region in all available family members.…”

Section: Discussionmentioning

confidence: 81%

Mutations at KCNQ1 and an unknown locus cause long QT syndrome in a large Australian family: Implications for genetic testing

Summers

Bokil

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

A large Australian family affected with long QT syndrome (LQTS) was studied. The medical characteristics of the 16 clinically affected members were consistent with LQT1. A previously identified mutation in KCNQ1 was found in 12 affected individuals and 1 unaffected infant but absent in 4 affected family members. A haplotype consisting of specific alleles for microsatellites flanking in KCNQ1 was associated with the mutation. This was absent from the four affected individuals without the mutation, who had three different haplotypes in this region, indicating that LQTS is unlikely to be segregating with KCNQ1 in these anomalous family members. A genome scan revealed 12 regions where all four of these individuals shared alleles. One region on chromosome 21 contained the KCNE1, KCNE2, KCNJ6, and KCNJ15 genes. A common variant of KCNE1 was segregating in the family but did not explain the anomalous cases. A candidate region on chromosome 7 contained the AKAP9 and KCND2 genes. A previously reported mutation in the N-terminal Yotiao region of AKAP9 was absent from the family. No evidence was found implicating any other known or suspected LQTS gene. This family shows that there remain unidentified genetic causes of LQTS which are clinically significant and highlights the difficulties associated with genetic testing in LQTS, since we cannot rule out risk in individuals who are negative for the known mutation in KCNQ1 without knowing the second disease locus.

show abstract

Section: Discussionmentioning

confidence: 81%

Mutations at KCNQ1 and an unknown locus cause long QT syndrome in a large Australian family: Implications for genetic testing

Summers

Bokil

et al. 2010

American J of Med Genetics Pt A

View full text Add to dashboard Cite

show abstract

The genetic basis of long QT and short QT syndromes: A mutation update

et al. 2009

View full text Add to dashboard Cite

Long QT and short QT syndromes (LQTS and SQTS) are cardiac repolarization abnormalities that are characterized by length perturbations of the QT interval as measured on electrocardiogram (ECG). Prolonged QT interval and a propensity for ventricular tachycardia of the torsades de pointes (TdP) type are characteristic of LQTS, while SQTS is characterized by shortened QT interval with tall peaked T-waves and a propensity for atrial fibrillation. Both syndromes represent a high risk for syncope and sudden death. LQTS exists as a congenital genetic disease (cLQTS) with more than 700 mutations described in 12 genes (LQT1-12), but can also be acquired (aLQTS). The genetic forms of LQTS include Romano-Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal dominant pattern of inheritance, and syndromes with LQTS in association with other conditions. The latter includes Jervell and Lange-Nielsen syndrome (JLNS), Andersen syndrome (AS), and Timothy syndrome (TS). The genetics are further complicated by the occurrence of double and triple heterozygotes in LQTS and a considerable number of nonpathogenic rare polymorphisms in the involved genes. SQTS is a very rare condition, caused by mutations in five genes (SQTS1-5). The present mutation update is a comprehensive description of all known LQTS-and SQTS-associated mutations.

show abstract

Genetics in Critical Care: A Toolbox

Beery

2008

Critical Care Nursing Clinics of North America

View full text Add to dashboard Cite

A Candidate Locus Approach Identifies a Long QT Syndrome Gene Mutation

Cited by 5 publications

References 16 publications

Mutations at KCNQ1 and an unknown locus cause long QT syndrome in a large Australian family: Implications for genetic testing

Mutations at KCNQ1 and an unknown locus cause long QT syndrome in a large Australian family: Implications for genetic testing

The genetic basis of long QT and short QT syndromes: A mutation update

Genetics in Critical Care: A Toolbox

Contact Info

Product

Resources

About