Leber hereditary optic neuropathy (LHON) is a maternally inherited disorder characterized by a bilateral acute or subacute painless central visual loss in young adults, predominately in males.So far no one theory can completely explain all clinical manifestations of LHON.

This study was to investigate whether there is a linkage between X-chromosomal and mitochondrial mutation in the inheritance of a Chinese LHON pedigree with only male patients.

This study was approved by Ethic Committee of Affiliated First Hospital of Zhengzhou University and followed by Declaration of Helsinki.A Chinese LHON pedigree was included in Anyang city from January 2008 to August 2016.Periphery blood of 5-10 ml was collected from 4 sufferers, 13 maternal members and 10 non-maternal members for DNA extraction and PCR sequencing.The gene scanning and genotyping analysis were performed by ABI-PRISM 3100 genetic analyzer and Genotyper 3.7 software, and linkage analysis was carried out with Linkage software for the calculation of logarithm of odds (LOD). Mitochondrial DNA (mtDNA) sequence, fluorescence-based Genescan for X- chromosomal sequence were analyzed in the propositus and haplotype was evaluated.

A total of 5 generations and 71 families were included in the pedigree, with 6 male sufferers, 30 maternal members and 41 non-maternal members.The visual acuity was ≤0.10, and the central visual field defection, the optic nerve flushing was found in the acute phase, different levels of the optic nerve fibers atrophy were found in the chronic phase; visual evoked potential (VEP) amplitude was low and peak latency were found in the male patients, and no any ocular abnormality was seen in the maternal members, meeting a maternally inherited characteristics, with the penetrance of 20%.The three primary mutations were not been found in this family by PCR sequencing.mtDNA sequencing appeared 31 variation of loci in the proband, including a known G3635A mutation, as well as an unknown ND5 A12340G missense mutation and ND4 T11809C synonymous mutation as well as 28 polymorphism of locus, and the proband was mitochondrial haplotype F1.The maternal families were mutation carriers of G3635A and A12340G loci, while the same mutation was not found in the normal family members and 107 controls.The maximum two point parametric LOD score was 1.46(θ=0.0) for marker DXS1060, located at Xp22.3, and the two-point and multipoint non-parametric linkage analysis were significant (all at P>0.05).

The ND5 A12340G and ND1 G3635A mutations coexist in this LHON family, and the ND5 A12340G mutation is a newly reported mutation.There is no evidence for an X-linked modifiers loci in this Chinese LHON family.

Leber hereditary optic neuropathy/genetics; X-linked modifiers locus; Microsatellite marker; Parametric linkage analysis; Non-parametric linkage analysis