Haplogroup heterogeneity of LHON patients carrying the m.14484T>C mutation in India.
Invest Ophthalmol Vis Sci
; 54(6): 3999-4005, 2013 Jun 10.
Article
en En
| MEDLINE
| ID: mdl-23674761
ABSTRACT
PURPOSE:
To investigate the clinical and mitochondrial DNA (mtDNA) haplogroup background of Indian Leber hereditary optic neuropathy (LHON) patients carrying the m.14484T>C mutation.METHODS:
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.RESULTS:
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 = 133). 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.CONCLUSIONS:
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
ADN Mitocondrial
/
Mutación Puntual
/
Atrofia Óptica Hereditaria de Leber
/
NADH Deshidrogenasa
Límite:
Adult
/
Female
/
Humans
/
Male
País/Región como asunto:
Asia
Idioma:
En
Año:
2013
Tipo del documento:
Article