Journal article

Publication year: 2019

Pages: 282-289

Journal: Clinical Research in Cardiology

Volume number: 108

Issue number: 3

ISSN: 1861-0684

eISSN: 1861-0692

DOI Link: https://doi.org/10.1007/s00392-018-1354-8

Publisher: Springer

Abstract: 
BackgroundPrevious investigations assessing the genetic cause of pediatric hypertrophic cardiomyopathy (HCM) found underlying genetic mutations in 50-60% of cases. The purpose of our study was to analyze whether this number can be augmented by applying next-generation sequencing and directing further diagnostics by discussing unsolved cases in a multidisciplinary board.Methods and results42 patients with the diagnoses of HCM made before age 18years were treated in our center from 2000 to 2016. Genetic analysis was performed in 36 subjects, a genetic defect was detected in 29 (78%) patients. 15 individuals (42%) had pathogenic variants in genes encoding sarcomere proteins, and 5 (14%) in genes coding for components of the RAS/MAPK signaling pathway. 4 subjects (11%) had mutations in the GAA gene (Pompe disease), and 3 (8%) had Frataxin repeat expansions (Friedreich's ataxia). One patient each showed a mutation in BAG3 and LMNA. Discussion of unsolved HCM cases after performing next-generation sequencing (28 genes) in an interdisciplinary board unraveled the genetic cause in 9 subjects (25%).ConclusionA definite genetic diagnosis can be reached in nearly 80% with HCM of childhood onset. Next-generation sequencing in conjunction with a multidisciplinary cooperation can enhance the diagnostic yield substantially. This may be important for risk stratification, treatment planning and genetic counseling.

Harvard Citation style: Rupp, S., Felimban, M., Schaenzer, A., Schranz, D., Marschall, C., Zenker, M., et al. (2019) Genetic basis of hypertrophic cardiomyopathy in children, Clinical Research in Cardiology, 108(3), pp. 282-289. https://doi.org/10.1007/s00392-018-1354-8

APA Citation style: Rupp, S., Felimban, M., Schaenzer, A., Schranz, D., Marschall, C., Zenker, M., Logeswaran, T., Neuhaeuser, C., Thul, J., Jux, C., & Hahn, A. (2019). Genetic basis of hypertrophic cardiomyopathy in children. Clinical Research in Cardiology. 108(3), 282-289. https://doi.org/10.1007/s00392-018-1354-8