Unknown

Dataset Information

0

Extremely low penetrance of Leber's hereditary optic neuropathy in 8 Han Chinese families carrying the ND4 G11778A mutation.


ABSTRACT:

Purpose

To investigate the role of mitochondrial haplotypes in the development of Leber's hereditary optic neuropathy (LHON) associated with the ND4 G11778A mutation in Chinese families.

Design

Eight Han Chinese families with maternally transmitted LHON were studied using clinical, genetic, and molecular evaluations.

Participants

One hundred sixty-seven subjects from 8 Chinese families with a wide age range and severity of visual impairment.

Methods

All subjects underwent the clinical and genetic evaluation, as well as molecular analysis of mitochondrial DNA (mtDNA).

Main outcome measures

The ophthalmologic examinations included visual acuity, visual field examination, visual evoked potentials, and fundus photography. Mitochondrial DNA analysis included the polymerase chain reaction amplification of the entire mtDNA and subsequent sequence determination.

Results

Eight families exhibited extremely low penetrance of visual impairment, with the average of 13%. In particular, 14 (12 males and 2 females) of 119 matrilineal relatives in these families exhibited the variable severity and age at onset in visual dysfunction. The average age of onset of vision loss was 17 years. Molecular analysis of mtDNA identified the homoplasimic ND4 G11778A mutation and distinct sets of variants belonging to the Asian haplogroups M8a2, D4g2, B4a1c, B5b, N9a1, D4b2b, C, and M7b1. However, there was an absence of secondary LHON-associated mtDNA mutations in these 8 Chinese families.

Conclusions

The extremely low penetrance of vision loss in these 8 Chinese pedigrees strongly indicates that the G11778A mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggest that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the G11778A mutation in those Chinese families with very low penentrace of vision loss. However, nuclear backgrounds and environmental factors seem to be modifying factors for the phenotypic manifestation of the G11778A mutation in these Chinese families.

SUBMITTER: Qu J 

PROVIDER: S-EPMC2907161 | BioStudies | 2009-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3340853 | BioStudies
2007-01-01 | S-EPMC2014724 | BioStudies
2010-01-01 | S-EPMC2906641 | BioStudies
2010-01-01 | S-EPMC3066600 | BioStudies
2010-01-01 | S-EPMC2826595 | BioStudies
2010-01-01 | S-EPMC2839065 | BioStudies
2011-01-01 | S-EPMC3244475 | BioStudies
2014-01-01 | S-EPMC4266137 | BioStudies
2020-01-01 | S-EPMC7456240 | BioStudies
2014-01-01 | S-EPMC4249950 | BioStudies