Cited 13 times since 2017 (2 per year) source: EuropePMC Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation, Volume 25, Issue 12, 1 1 2017, Pages 675-681 A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects. van der Linde IHM, Hiemstra YL, Bökenkamp R, van Mil AM, Breuning MH, Ruivenkamp C, Ten Broeke SW, Veldkamp RF, van Waning JI, van Slegtenhorst MA, van Spaendonck-Zwarts KY, Lekanne Deprez RH, Herkert JC, Boven L, van der Zwaag PA, Jongbloed JDH, Bootsma M, Barge-Schaapveld DQCM
Background
Mutations in the myosin heavy chain 7 (MYH7) gene commonly cause cardiomyopathy but are less frequently associated with congenital heart defects.
Methods
In this study, we describe a mutation in the MYH7 gene, c. 5754C > G; p. (Asn1918Lys), present in 15 probands and 65 family members.
Results
Of the 80 carriers (age range 0-88 years), 46 (57.5%) had cardiomyopathy (mainly dilated cardiomyopathy (DCM)) and seven (8.8%) had a congenital heart defect. Childhood onset of cardiomyopathy was present in almost 10% of carriers. However, in only a slight majority (53.7%) was the left ventricular ejection fraction reduced and almost no arrhythmias or conduction disorders were noted. Moreover, only one carrier required heart transplantation and nine (11.3%) an implantable cardioverter defibrillator. In addition, the standardised mortality ratio for MYH7 carriers was not significantly increased. Whole exome sequencing in several cases with paediatric onset of DCM and one with isolated congenital heart defects did not reveal additional known disease-causing variants. Haplotype analysis suggests that the MYH7 variant is a founder mutation, and is therefore the first Dutch founder mutation identified in the MYH7 gene. The mutation appears to have originated in the western region of the province of South Holland between 500 and 900 years ago.
Conclusion
Clinically, the p. (Asn1918Lys) mutation is associated with congenital heart defects and/or cardiomyopathy at young age but with a relatively benign course.
