Macular Pattern Retinal Dystrophy, Adult-onset Diabetes, and Deafness: A Family Study of A3243G Mitochondrial Heteroplasmy

Purpose To correlate mitochondrial DNA (mtDNA) mutation with phenotypic expression in three members of a Finnish family with macroreticular pattern dystrophy, non-insulin-dependent diabetes mellitus, and deafness. Methods A multiplex polymerase chain reaction/allele-specific oligonucleotide method was used to screen 10 mtDNA point mutations known to cause mitochondrial DNA disorders, often characterized by myopathy, retinopathy, or both. Quantitative analysis of mutant mitochondrial DNA was performed in three tissue types in each of three family members by determining the percentage of mutant mtDNA in blood, buccal cells, and hair follicles. Results A heteroplasmic A3243G mtDNA point mutation was found in each of the three family members studied. Heteroplasmy refers to the coexistence of normal and mutant mitochondria in the same cell. The average percentage of mutant heteroplasmy ranged from 11% to 25%. The severity of disease symptoms did not appear to correlate with the average degree of mutant heteroplasmy in the three tissues analyzed. Conclusions Molecular confirmation in this family emphasizes the importance of mitochondrial DNA mutation analysis in patients with macular pattern retinal dystrophy and other mitochondrial associated nonocular diseases, such as non-insulin-dependent diabetes mellitus and deafness. The detection of a disease-associated mitochondrial DNA mutation warrants genetic counseling, appropriate patient follow-up, and possibly the molecular testing of other at-risk family members.