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OPA1 mutations and mitochondrial DNA haplotypes in autosomal dominant optic atrophy.

Authors: Han, J  Thompson-Lowrey, AJ  Reiss, A  Mayorov, V  Jia, H  Biousse, V  Newman, NJ  Brown, MD 
Citation: Han J, etal., Genet Med. 2006 Apr;8(4):217-25.
Pubmed: (View Article at PubMed) PMID:16617242
DOI: Full-text: DOI:10.109701.gim.0000214299.61930.c0

PURPOSE: Autosomal dominant optic atrophy is a form of blindness, due in part to mutations affecting the mitochondrial-targeted OPA1 gene product. Both OPA1-positive and OPA1-negative families exhibit variable expressivity and incomplete penetrance. The purpose of this study was therefore to determine if the background mtDNA genotype acts as a genetic modifier for the expression of this disease. METHODS: To find novel pathogenic OPA1 mutations, we performed complete OPA1 gene exon sequencing in 30 patients. To assess the possibility that mitochondrial DNA haplotype acts as a genetic modifier, we determined the mitochondrial DNA haplotype in 29 Caucasian OPA1-positive and OPA1-negative patients. Deviations in haplotype distribution between patient and control groups were determined by statistical means. RESULTS: Seven new pathogenic OPA1 mutations were found. Most were detected in the mitochondrial targeting N-terminus or in the coiled-coil domain at the C-terminus. Mitochondrial DNA haplotype analysis indicated that the European haplogroup distribution was different between Caucasian patients and controls. Further, haplogroup J was three-fold over-represented in OPA1-negative patients. CONCLUSIONS: Overall, our results support haploinsufficiency as a genetic mechanism in OPA1-positive cases and also suggest that mtDNA genetic background may influence disease expression in a subset of cases.


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RGD Object Information
RGD ID: 7800699
Created: 2014-01-16
Species: All species
Last Modified: 2014-01-16
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.