title: Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?
abstract: Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We describe a family in which members carry either a single mutation or are double heterozygous for mutations in myosin heavy chain gene (MYH7) and cysteine and glycine-rich protein 3 (CSRP3). The described family emphasises the idea of a more severe clinical phenotype with double-heterozygous mutations. It also highlights the importance of cardiological screening where NT-proBNP may serve as an added diagnostic tool.Conclusion. With a more severe inexplicable phenotype of HCM within a family, one should consider the possibility of double-heterozygous mutations. This implies that in such families, even when one disease-causing mutation is found, all the family members still have an implication for cardiological screening parallel to extended genetic screening. (Neth Heart J 2009;17:458-63.).
authors.affiliation: Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: I A W
authors.initials: IA
authors.lastname: van Rijsingen
authors.forename: J F
authors.initials: JF
authors.lastname: Hermans-van Ast
authors.forename: Y H J M
authors.initials: YH
authors.lastname: Arens
authors.forename: S M
authors.initials: SM
authors.lastname: Schalla
authors.forename: C E M
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: A
authors.initials: A
authors.lastname: van den Wijngaard
authors.forename: Y M
authors.initials: YM
authors.lastname: Pinto