Journal article
Identification of A gene responsible for familial wolff-parkinson-white syndrome
The New England journal of medicine, Vol.344(24), pp.1823-1831
2001
DOI: 10.1056/NEJM200106143442403
PMID: 11407343
Abstract
Background: The Wolff-Parkinson-White syndrome, with a prevalence in Western countries of 1.5 to 3.1 per 1000 persons, causes considerable morbidity and may cause sudden death. We identified two families in which the Wolff-Parkinson-White syndrome segregated as an autosomal dominant disorder.
Methods: We studied 70 members of the two families (57 in Family 1 and 13 in Family 2). The subjects underwent 12-lead electrocardiography and two-dimensional echocardiography. Genotyping mapped the gene responsible to 7q34-q36, a locus previously identified to be responsible for an inherited form of Wolff-Parkinson-White syndrome. Candidate genes were identified, sequenced, and analyzed in normal and affected family members to identify the disease-causing gene.
Results: A total of 31 members (23 from Family 1 and 8 from Family 2) had the Wolff-Parkinson-White syndrome. Affected members of both families had ventricular preexcitation with conduction abnormalities and cardiac hypertrophy. The maximal combined two-point lod score was 9.82 at a distance of 5 cM from marker D7S636, which confirmed the linkage of the gene in both families to 7q34-q36. Haplotype analysis indicated that there were no alleles in common in the two families at this locus, suggesting that the two families do not have a common founder. We identified a missense mutation in the gene that encodes the gamma2 regulatory subunit of AMP-activated protein kinase (PRKAG2). The mutation results in the substitution of glutamine for arginine at residue 302 in the protein.
Conclusions: The identification of this genetic defect has important implications for elucidating the pathogenesis of ventricular preexcitation. Further understanding of how this molecular defect leads to supraventricular arrhythmias could influence the development of specific therapies for other forms of supraventricular arrhythmia.
Details
- Title: Subtitle
- Identification of A gene responsible for familial wolff-parkinson-white syndrome
- Creators
- Michael H GOLLOB - Section of Cardiology, Baylor College of Medicine, Houston, United StatesMartin S GREEN - University of Ottawa Heart Institute, Ottawa, Ont, CanadaLinda L BACHINSKI - Section of Cardiology, Baylor College of Medicine, Houston, United StatesRobert ROBERTS - Section of Cardiology, Baylor College of Medicine, Houston, United StatesAnthony S.-L TANG - University of Ottawa Heart Institute, Ottawa, Ont, CanadaTanya GOLLOB - Section of Cardiology, Baylor College of Medicine, Houston, United StatesAkihiko KARIBE - Section of Cardiology, Baylor College of Medicine, Houston, United StatesAl-Sayegh HASSAN - University of Ottawa Heart Institute, Ottawa, Ont, CanadaFerhaan AHMAD - Section of Cardiology, Baylor College of Medicine, Houston, United StatesRyan LOZADO - Section of Cardiology, Baylor College of Medicine, Houston, United StatesGopi SHAH - Section of Cardiology, Baylor College of Medicine, Houston, United StatesLameh FANANAPAZIR - University of Ottawa Heart Institute, Ottawa, Ont, Canada
- Resource Type
- Journal article
- Publication Details
- The New England journal of medicine, Vol.344(24), pp.1823-1831
- DOI
- 10.1056/NEJM200106143442403
- PMID
- 11407343
- NLM abbreviation
- N Engl J Med
- ISSN
- 0028-4793
- eISSN
- 1533-4406
- Publisher
- Massachusetts Medical Society; Boston, MA
- Language
- English
- Date published
- 2001
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9984025596802771
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