Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?
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.).
van Rijsingen
I A W
IA
Department of Cardiology, Maastricht University Medical Center, Maastricht, the Netherlands.
Hermans-van Ast
J F
JF
Arens
Y H J M
YH
Schalla
S M
SM
de Die-Smulders
C E M
CE
van den Wijngaard
A
A
Pinto
Y M
YM