title: Wenckebach periodicity at rest that normalizes with tachycardia in a family with a NKX2.5 mutation.
abstract: A family with asymptomatic Wenckebach atrioventricular block (Wenckebach periodicity [WP]) has been followed at the investigators' institution for >4 decades. In contrast to all reported cases of WP (except in top-ranking athletes) family members have WP at rest that promptly converts to regular sinus tachycardia with exercise. They also have mild apical noncompaction that has been quite stable. Because of apparent autosomal dominant inheritance of the structural and arrhythmia disorders, deoxyribonucleic acid was obtained from 4 affected family members in 2 generations for sequence analysis of the cardiac transcription factor gene NKX2.5. A novel frame-shift mutation (c.959delC) was identified that would result in premature truncation of the protein at residue 293, with loss of the C-terminal 31 amino acids. The responsiveness of WP to exercise, the long-term stability of the WP rhythm, and the mild asymptomatic structural features expand the phenotypic presentation of diseases related to mutations in NKX2.5. In addition, the physiology of WP is reviewed in these subjects and in highly conditioned athletes. In conclusion, the investigators report familial stable WP and ventricular noncompaction caused by a mutation in NKX2.5.
authors.affiliation: Division of Cardiology, Department of Pediatrics, University of Washington, Seattle, Washington, USA. wgg@uw.edu
authors.forename: Warren
authors.initials: W
authors.lastname: Guntheroth
authors.forename: Lani
authors.initials: L
authors.lastname: Chun
authors.forename: Kristen K
authors.initials: KK
authors.lastname: Patton
authors.forename: Mark M
authors.initials: MM
authors.lastname: Matsushita
authors.forename: Richard L
authors.initials: RL
authors.lastname: Page
authors.forename: Wendy H
authors.initials: WH
authors.lastname: Raskind
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054537:Atrioventricular Block / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D012146:Rest / Q000502:physiology*; D013610:Tachycardia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
chemical_list: D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D014157:Transcription Factors; D004247:DNA