Mitochondrial Genome Screening Identified 26 Novel Variants in Children with Nonsyndromic Congenital Hearing Impairment

Author(s): Hema Bindu L, Shehnaz Sultana, Penagaluru Pardhanandana Reddy

Background: Mitochondrial DNA (mtDNA) mutations may be responsible for the pathogenesis of maternally inherited hearing loss in both nonsyndromic and syndromic condition. Several mitochondrial genes, including genes coding for rRNA, tRNA, and respiratory chain complex subunits and protein coding genes play significant role in nonsyndromic deafness.

Materials and Methods: 175 children with congenital hearing impairment and 92 normal subjects were screened for 13 mitochondrial genes comprising of two small ribosomal genes (12S rRNA and 16S rRNA), 7 tRNA genes (tRNA Val, tRNA Leu (UUR), tRNA Ile, tRNA Gln, tRNA Met, tRNA Ser (UCN) and tRNA Asp) and 4 protein coding genes (NADH dehydrogenase 1, NADH dehydrogenase 2, Cytochrome Oxidase I and Cytochrome Oxidase II) genes using specific sets of overlapping oligonucleotide primers for amplification.

Results: A total of 26 novel variations were observed in the present study. 8 of them were in the protein coding ND1 gene, 2 in ND2 gene, 6 in ribosomal 12S rRNA, 1 in ribosomal 16S rRNA, 5 in COII and 4 in COI genes. Three variants, each belonging to ND1 (3456T/G), COI (6140C/A) and COII (8115G/A) genes were found to be heteroplasmic. Out of 26, 8 variants were observed to be transversions and 11 as transitions. Out of 19 novel variants of protein coding genes, 3 missense (A3652G, G7830A, 8115G/A) mutations and 16 silent mutations were observed.

Conclusion: This study demonstrated that various mitochondrial genes including protein-coding genes might be responsible for nonsyndromic deafness, providing new insights on the molecular bases of this pathology.