MACULAR PATTERN RETINAL DYSTROPHY, ADULT-ONSET DIABETES, AND DEAFNESS- A FAMILY STUDY OF A3243G MITOCHONDRIAL HETEROPLASMY

PURPOSE: To correlate mitochondrial DNA (mtDNA) mutation with phenotyp ic expression in three members of a Finnish family with macroreticular pattern dystrophy, non-insulin dependent diabetes mellitus, and deafn ess. METHODS: A multiplex polymerase chain reaction/allele-specific ol igonucleotide 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 member s by determining the percentage of mutant mtDNA in blood, buccal cells , and hair follicles. RESULTS: A heteroplasmic A3243G mtDNA point muta tion was found in each of the three family members studied, Heteroplas my refers to the coexistence of normal and mutant mitochondria in the same cell, The average percentage of mutant heteroplasmy ranged from 1 1% to 25%. The severity of disease symptoms did not appear to correlat e with the average degree of mutant heteroplasmy in the three tissues analyzed. CONCLUSIONS: Molecular confirmation in this family emphasize s the importance of mitochondrial DNA mutation analysis in patients wi th macular pattern retinal dystrophy and other mitochondrial associate d 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, a nd possibly the molecular testing of other at-risk family members.