A Dutch MYH7 founder mutation, p.(Asn1918Lys), is associated with early onset cardiomyopathy and congenital heart defects
| Autor: | Ludolf G. Boven, Marianne Bootsma, Y. L. Hiemstra, Regina Bökenkamp, Johanna C. Herkert, A. M. van Mil, R. F. Veldkamp, R. H. Lekanne Deprez, J. I. van Waning, I. H. M. van der Linde, S. W. ten Broeke, Daniela Q.C.M. Barge-Schaapveld, P. A. van der Zwaag, Jan D. H. Jongbloed, Martijn H. Breuning, Claudia A. L. Ruivenkamp, K. Y. van Spaendonck-Zwarts, M. van Slegtenhorst |
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| Přispěvatelé: | Human Genetics, ARD - Amsterdam Reproduction and Development, Other departments, ACS - Pulmonary hypertension & thrombosis, Erasmus MC other, Clinical Genetics, Cardiovascular Centre (CVC) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty GENES Cardiomyopathy medicine.medical_treatment 030204 cardiovascular system & hematology DIAGNOSTICS DISEASE 03 medical and health sciences 0302 clinical medicine Internal medicine Medicine BICUSPID AORTIC-VALVE Founder mutation Exome sequencing Heart transplantation Ejection fraction HYPERTROPHIC CARDIOMYOPATHY business.industry Congenital heart defect Hypertrophic cardiomyopathy Dilated cardiomyopathy LEFT-VENTRICULAR NONCOMPACTION Implantable cardioverter-defibrillator medicine.disease 030104 developmental biology Cardiology MYH7 Original Article GENOTYPE-PHENOTYPE Cardiology and Cardiovascular Medicine business Beta myosin heavy chain 7 |
| Zdroj: | Netherlands heart journal, 25(12), 675-681. Bohn Stafleu van Loghum Netherlands Heart Journal, 25(12), 675-681. Bohn Stafleu van Loghum Netherlands Heart Hournal, 25(12), 675-681. Bohn, Stafleu, Van Loghum Netherlands Heart Journal, 25(12), 675-681 Netherlands Heart Journal |
| ISSN: | 1568-5888 |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1007/s12471-017-1037-5) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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