RT Journal Article
SR Electronic
T1 Identification of known and unknown genes associated with mitral valve prolapse using an exome slice methodology
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 843
OP 850
DO 10.1136/jmedgenet-2019-106715
VO 57
IS 12
A1 Aniek L van Wijngaarden
A1 Yasmine L Hiemstra
A1 Tamara T Koopmann
A1 Claudia A L Ruivenkamp
A1 Emmelien Aten
A1 Martin J Schalij
A1 Jeroen J Bax
A1 Victoria Delgado
A1 Daniela Q C M Barge-Schaapveld
A1 Nina Ajmone Marsan
YR 2020
UL http://jmg.bmj.com/content/57/12/843.abstract
AB Purpose Although a familial distribution has been documented, the genetic aetiology of mitral valve prolapse (MVP) is largely unknown, with only four genes identified so far: FLNA, DCHS1, DZIP1 and PLD1. The aim of this study was to evaluate the genetic yield in known causative genes and to identify possible novel genes associated with MVP using a heart gene panel based on exome sequencing.Methods Patients with MVP were referred for genetic counselling when a positive family history for MVP was reported and/or Barlow’s disease was diagnosed. In total, 101 probands were included to identify potentially pathogenic variants in a set of 522 genes associated with cardiac development and/or diseases.Results 97 (96%) probands were classified as Barlow’s disease and 4 (4%) as fibroelastic deficiency. Only one patient (1%) had a likely pathogenic variant in the known causative genes (DCHS1). However, an interesting finding was that 10 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: DSP (1×), HCN4 (1×), MYH6 (1×), TMEM67 (1×), TRPS1 (1×) and TTN (5×).Conclusion Exome slice sequencing analysis performed in MVP probands reveals a low genetic yield in known causative genes but may expand the cardiac phenotype of other genes. This study suggests for the first time that also genes related to cardiomyopathy may be associated with MVP. This highlights the importance to screen these patients and their family for the presence of arrhythmias and of ‘disproportionate’ LV remodelling as compared with the severity of mitral regurgitation, unravelling a possible coexistent cardiomyopathy.