Autosomal recessive catecholamine- or exercise-induced polymorphic ventricular tachycardia: clinical features and assignment of the disease gene to chromosome 1p13-21.
Circulation
; 103(23): 2822-7, 2001 Jun 12.
Article
in En
| MEDLINE
| ID: mdl-11401939
ABSTRACT
BACKGROUND:
Catecholaminergic polymorphic ventricular tachycardia (PVT) is characterized by episodes of syncope, seizures, or sudden death in response to physiological or emotional stress. In 2 families with autosomal dominant inheritance, the disease gene was mapped to chromosome 1q42-43. The objectives of this study were to characterize the clinical features of the disease in a Bedouin tribe from Israel and to map the disease gene. METHODS ANDRESULTS:
In this Bedouin tribe, 9 children (age, 7+/-4 years) from 7 related families have died suddenly during the past decade, and 12 other children suffered from recurrent syncope and seizures starting at the age of 6+/-3 years. Parents of affected individuals were asymptomatic and were all related (first-, second-, or third-degree cousins). Segregation analysis suggested autosomal recessive inheritance. All 12 symptomatic patients and 1 asymptomatic sibling (mean age, 13+/-7 years) were found to have a relative resting bradycardia (64+/-13 bpm, versus 93+/-12 bpm in the unaffected siblings), as well as PVT induced by treadmill or isoproterenol infusion and appearing at a mean sinus rate of 110+/-10 bpm. Patients responded favorably to treatment with beta-blockers. A genome-wide search using polymorphic DNA markers mapped the disease locus to a 16-megabase interval on chromosome 1p13-21. A maximal lod score of 8.24 was obtained with D1S189 at theta=0.00. Sequencing of KCND3, a gene that encodes an I(tO) potassium channel transporter, did not reveal any significant sequence alterations.CONCLUSIONS:
This unique form of autosomal recessive PVT affects young children and may be lethal if left untreated. Linkage analysis maps this disorder to chromosome 1p13-21.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Chromosomes, Human, Pair 1
/
Catecholamines
/
Tachycardia, Ventricular
/
Arabs
/
Physical Exertion
Type of study:
Diagnostic_studies
Limits:
Adolescent
/
Child
/
Humans
Country/Region as subject:
Asia
Language:
En
Journal:
Circulation
Year:
2001
Document type:
Article