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Nahid Akhtar Khan, Periyasamy Govindaraj, Nagasamy Soumittra, Sundaramoorthy Srilekha, Selvakumar Ambika, Ayyasamy Vanniarajan, Angamuthu K. Meena, Megha S. Uppin, Challa Sundaram, Arun B. Taly, Parayil Sankaran Bindu, Narayanappa Gayathri, Kumarasamy Thangaraj; Haplogroup Heterogeneity of LHON Patients Carrying the m.14484T>C Mutation in India. Invest. Ophthalmol. Vis. Sci. 2013;54(6):3999-4005. doi: https://doi.org/10.1167/iovs.13-11925.
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To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber hereditary optic neuropathy (LHON) patients carrying the m.14484T>C mutation.
Detailed clinical investigation and complete mtDNA sequencing analysis was carried out for eight Indian LHON families with the m.14484T>C mutation. Haplogroup was constructed based on the evolutionarily important mtDNA variants.
In the present study, we characterized eight unrelated probands selected from 187 LHON cases. The overall penetrance of the disease was estimated to be 19.75% (16/81) in eight pedigrees with the m.14484T>C mutation and showed substantially higher sex bias (male:female = 13:3). The mtDNA haplogrouping revealed that they belong to diverse haplogroups; i.e., F1c1, M31a, U2a, M*, I1, M6, M3a1, and R30a. Interestingly, we did not find an association of the m.14484T>C mutation with any specific haplogroup within the Indian population. We also did not find any secondary mutation(s) in these pedigrees, which might affect the clinical expression of LHON.
Contrary to earlier reports showing preferential association of the m.14484T>C mutation with western Eurasian haplogroup J and increased clinical penetrance when present in J1 subhaplogroup background, the present study shows that m.14484T>C arose independently in a different mtDNA haplogroup and ethnic background in India, which may influence the clinical expression of the disease.
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