Transition m.3308T>C in the ND1 gene is associated with left ventricular hypertrabeculation/noncompaction

Though left ventricular hypertrabeculation/noncompaction (LVNC) is frequently associated with mitochondrial DNA (mtDNA) mutations, it has not been reported in association with the transition m.3308T>C of the NADH dehydrogenase subunit 1 (ND1) gene. The index patient is a 16-year-old Tunisian female who was investigated for a systolic murmur and cardiomegaly. Echocardiography revealed tricuspid insufficiency, moderate left ventricular dilatation, Ebstein's anomaly, a superior caval vein draining into the coronary sinus and, surprisingly, LVNC of the apex and the lateral wall. LVNC was absent in all other cardiologically investigated siblings. RNA and mtDNA sequence analysis revealed the known homoplasmic mutation m.3308T>C resulting in the replacement of the first amino acid methionine by threonine in the ND1 subunit of respiratory chain complex I. The m.3308T>C mutation was also present in the patient's mother and several other family members but absent in 350 controls. Additionally, the index patient carried the polymorphisms m.8248A>G in the COX2 gene and m.8468C>T in the ATP8 gene. It is concluded that LVNC may be associated with the known homoplasmic m.3308T>C mutation in the ND1 gene. However, the pathogenetic role of this mutation in the development of LVNC remains elusive.