Search

Background Ebstein9s anomaly is a rare congenital heart malformation characterised by adherence of the septal and posterior leaflets of the tricuspid valve to the underlying myocardium. As there have been reports of abnormal left ventricular morphology and function in patients with Ebstein9s anomaly we hypothesised that mutations in the β-myosin heavy chain (MYH7) may be associated with Ebstein9s anomaly. Methods MYH7 mutation analysis was undertaken in 141 unrelated affected individuals with Ebstein9s anomaly using next-generation sequencing on the 454 platform. 64 probands had no associated cardiac anomalies. The most common associated cardiac malformation were atrial septal defect (48 probands) and left ventricular non-compaction (LVNC) (7 probands). Where mutations were discovered, family studies were undertaken and the segregation of the mutation with disease was investigated. Results Heterozygous mutations were identified in eight of the probands including six of the seven with LVNC. Two patients had the same mutation; of the seven distinct mutations, five were novel (four missense changes and an in-frame deletion) and two have been previously reported in patients with hypertrophic cardiomyopathy. Family studies revealed additional members with LVNC for three of the probands, one of whom also had a relative with Ebstein9s anomaly. In these three pedigrees the mutation segregated with disease. Conclusions Mutations in MYH7 occur relatively frequently in Ebstein9s anomaly accompanied by LVNC. This study is another example of mutations in a sarcomere protein causing congenital heart malformation.

We thank Digilio et al for their interest in our paper, showing that 22q11.2 deletion syndrome (22q11.2DS) is underrecognised in adults with tetralogy of Fallot (TOF) and with pulmonary atresia (PA)/ventricular septal defect (VSD).1 Digilio et al disagree with our recommendation to consider genetic testing for the syndrome in all adults with TOF and PA/VSD. Rather they propose to reserve this for patients with associated ‘classic’ or ‘subtle’ extracardiac anomalies and to …