Left ventricular noncompaction is associated with mutations in the mitochondrial genome

Left ventricular noncompaction (LVNC) is a genetically heterogeneous condition and several nuclear loci have been associated with the defect. However, they only account for a small percentage of patients. Existing evidences suggest that pathogenic mitochondrial DNA (mtDNA) mutations and consequent mitochondrial malfunction can be an important component in the etiology of LVNC. To investigate if mtDNA mutation can serve as a primary cause for LVNC, complete nucleotide sequences of mitochondrial genomes from 20 LVNC patients were determined by Illumina parallel sequencing technology and analyzed by MitoMaster. Substitutions of a highly conserved Met31 in ND1 caused by rare mitochondrial single nucleotide polymorphisms (mtSNP) A3397G and T3398C were identified from two LVNC patients. Previously, T3398C has been reported from another LVNC patient, indicating mutations in Met31 in ND1 and resultant defects in complex I can be associated with LVNC. Additionally, three mtSNPs in protein-coding genes, seven variants in rRNA genes, and two transitions in tRNA genes were unrelated to the haplogroup and infrequent in the general population, suggesting that these mtSNPs could also be pathogenic. Our study revealed some mtSNPs could represent pathogenic mutations, lead to compromised mitochondrial function, and be associated with LVNC.