Wolfram (DIDMOAD) syndrome and Leber hereditary optic neuropathy (LHON) are associated with distinct mitochondrial DNA haplotypes.

摘要: Because Wolfram (or DIDMOAD) syndrome is supposed to be a mitochondrial (mt)-mediated disease, we investigated group of eight DIDMOAD patients with respect point mutations the mtDNA thus far described as being associated defined disorders such MELAS, MERRF, and LHON. Furthermore, screen for other defects used Southern blot analysis detect length rearrangements well PCR-SSCP direct sequencing all ND genes (complex I respiratory chain), 22 tRNAs, part cyt b gene unknown mutations. As disease control group, 17 LHON (harboring one primary mutations) were included in this study because overlapping clinical symptoms (optic atrophy) both syndromes. We compared variants identified those found consisting 67 healthy German blood donors. In total, was characterized by 29 polymorphic sites tRNA that define certain major Caucasian haplotypes. cluster nucleotide exchanges at positions (nps) 4216 11,251 roughly discriminates controls (12/67 controls, 18%) from groups (6/8 patients, 75%; 10/17 59%). All 4216-positive (10 patients) concentrated haplogroup additional nps 10,398, 12,612, 13,708 (haplogroup A), while bulk (5 distinct 4917, 10,463, 13,368, 14,233, 15,928. The frequencies haplogroups significantly lower versus respective groups. A more detailed performed two hypervariable regions noncoding D-loop region corroborated ranging haplogroups. Thus, different features here corresponded clusters variants, which might act predisposing haplotypes, increasing risk disease.