Molecular genetics in 1991 arrhythmia probands and 2782 relatives in Norway: Results from 17 years of genetic testing in a national laboratory

作者：Tonje Talsnes Stava, Knut Erik Berge, Kristina Hermann Haugaa, Marit Kristine Smedsrud, Trond P. Leren, Martin Prøven Bogsrud · 发表于：Clinical Genetics · 年份：2024 · DOI：10.1111/cge.14593 · 被引用次数：5 · 研究领域：Cardiac electrophysiology and arrhythmias、Cardiomyopathy and Myosin Studies、Cardiovascular Effects of Exercise

The aim of this study was to explore the prevalence of likely pathogenic or pathogenic variants and assess the diagnostic yield from genetic testing for cardiac arrhythmias in Norway since 2003. Data from 1991 probands and 2782 relatives were retrospectively collected from the laboratory information management system at Unit for Cardiac and Cardiovascular Genetics, Oslo University hospital. Of 1991 probands, 57.4% were females, age at genetic testing was 33.1 (±22.7) years, and 32.5% were under the age of 18. A likely pathogenic or pathogenic variant (including 14 novel) was detected in 15.4% in total. Of the 2782 relatives, 53.7% were females, age at genetic testing was 35.6 (±22.5) years, 27.3% were under the age of 18, and 45.3% carried the family variant. Probands and relatives combined, 1/3356 persons in the Norwegian population were heterozygous for an arrhythmia-causing variant. The founder variant p.Q530X (NM_000218.2: c.1588C>T) in KCNQ1 accounted for 34% of all variants in Norway. In conclusion, genetic testing provided a genetic basis of the arrhythmia in 15.4% of the probands. Familial cascade screening identified four times as many variant-positive relatives, allowing early detection and prompt stratification of arrhythmic risk of those variant carriers.