Analysis of mitochondrial DNA variations in Indian patients with congenital cataract.
OBJECTIVE
Identification of mitochondrial DNA (mtDNA) variations in the inherited cataract patients from south India.


METHODS
Three families with inherited cataract of maternal origin were evaluated. Clinical and ophthalmologic examinations were performed on available affected as well as unaffected family members. Samples of mtDNA were amplified using 24 pairs of overlapping primers to analyze the entire mitochondrial genome to screen for variations and analyzed for both coding and non-coding regions. Bioinformatic analysis was performed to evaluate the effect of nucleotide variations.


RESULTS
DNA sequence analysis of inherited cataract families showed 72 nucleotide variations, of which 15 were observed in the major non-coding D-loop region, 3 in the tRNA genes, 5 in the rRNA genes, and 49 in the protein coding region. Among these variations 56 were reported previously and 16 were novel of which, 12 synonymous substitutions, 2 non-synonymous substitutions along with a frameshift mutation, and one was in the non-coding region. Nicotinamide adenine dinucleotide dehydrogenase (NADH) subunit (ND) gene of mtDNA was highly altered, in general, and found to contain 4 variations specific for cataract patients of the first family, six for the second, and one for the third family.


CONCLUSIONS
Seventy-two variations were observed in three inherited cataract families. Four variations were specific for cataract patients of the first family, six for the second, and one for the third family. This is perhaps the first report on the presence of mitochondrial mutations in inherited cataracts.
Division of Biotechnology, Manipal Life Sciences Centre, Manipal University, Manipal, India.
Mascarenhas
M
Roshan
Shama Prasada
SP
Kabekkodu
Pai H
PH
Vijaya
Kamath
K
Manjunath
Jochen
J
Graw
P M
PM
Gopinath
Kapeattu
K
Satyamoorthy
D000328:Adult; D001483:Base Sequence; D002386:Cataract / Q000151:congenital / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020459:Genes, rRNA; D056426:Genetic Loci; D054629:Genome, Mitochondrial; D006239:Haplotypes; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009245:NADH Dehydrogenase / Q000235:genetics*; D016366:Open Reading Frames; D010375:Pedigree; D012343:RNA, Transfer / Q000235:genetics
D004272:DNA, Mitochondrial; C098483:NADH dehydrogenase subunit 4; D012343:RNA, Transfer; D009245:NADH Dehydrogenase