A novel mtDNA ND6 gene mutation associated with LHON in a Caucasian family |
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Authors: | Zhadanov Sergey I Atamanov Vasily V Zhadanov Nikolay I Oleinikov Oleg V Osipova Ludmila P Schurr Theodore G |
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Affiliation: | Department of Anthropology, University of Pennsylvania, Philadelphia, PA, USA. siz001@jefferson.edu |
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Abstract: | Leber's hereditary optic neuropathy (LHON) is a frequent cause of inherited blindness. A routine screening for common mtDNA mutations constitutes an important first in its diagnosis. However, a substantial number of LHON patients do not harbor known variants, both pointing to the genetic heterogeneity of LHON and bringing into question its genetic diagnosis. We report a familial case that exhibited typical features of LHON but lacked any of the common mutations. Genetic analysis revealed a novel pathogenic defect in the ND6 gene at 14279A that was not detected in any haplogroup-matched controls screened for it, nor has it been previously reported. This mutation causes a substantial conformational change in the secondary structure of the polypeptide matrix coil and may explain the LHON expression. Thus, it expands the spectrum of deleterious changes affecting ND6-encoding subunit and further highlights the functional significance of this gene, providing additional clues to the disease pathogenesis. |
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Keywords: | Complex I mtDNA Eye disorders Leber’s hereditary optic neuropathy |
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