Background: Leber’s Hereditary Optic Neuropathy (LHON) is a maternal inherited disease caused by mitochondrial DNA (mtDNA) mutations. The aim of the current study is to analysis the frequencies of mitochondrial ND1 G3460A, ND4 G11778A and ND6 T14484C mutations in patients with LHON.Methods: Our study enrolled 155 patients with LHON and 83 controls, PCR-Sanger sequencing was performed to screen the presence of these primary mutations. Moreover, we performed clinical, genetic and molecular characterizations of five Chinese families carrying LHON-related three primary mutations.Results: 28 patients with G3460A (18.1%), 86 patients with G11778A (55.5%) and 32 patients carrying T14484C mutation (20.6%) were identified. However, none of these primary mutations were identified in controls. Among them, one patient carrying G3460A, two patients with G11778A and two patients with T14484C mutation had an obvious family history of LHON. Clinical evaluation of these pedigrees showed the variable clinical phenotypes with different age at onset of LHON. Sequence analysis of the complete mtDNA genes from the matrilineal relatives suggested the presence of these primary mutations. However, the lack of any functional variants in mtDNA genes revealed that mitochondrial haplogroups or haplotypes may not play important roles in the clinical phenotypic manifestation of LHON-associated primary mutations.Conclusions: Our data indicated that screening for the mtDNA primary mutations was necessary for early detection, prevention and diagnosis of LHON.

Accurately recognizing pathogens by the host is vital for initiating appropriate immune response against infecting microorganisms. Caenorhabditis elegans has no known receptor to recognize pathogen-associated molecular pattern. However, recent studies showed that nematodes have a strong specificity for transcriptomes infected by different pathogens, indicating that they can identify different pathogenic microorganisms. However, the mechanism(s) for such specificity remains largely unknown. In this study, we showed that the nematophagous fungus Purpureocillium lavendulum can infect the intestinal tract of the nematode C. elegans and the infection led to the accumulation of reactive oxygen species (ROS) in the infected intestinal tract, which suppressed fungal growth. Co-transcriptional analysis revealed that fungal genes related to anaerobic respiration and ethanol production were up-regulated during infection. Meanwhile, the ethanol dehydrogenase Sodh-1 in C. elegans was also up-regulated. Together, these results suggested that the infecting fungi encounter hypoxia stress in the nematode gut and that ethanol may play a role in the host–pathogen interaction. Ethanol production in vitro during fungal cultivation in hypoxia conditions was confirmed by gas chromatography-mass spectrometry. Direct treatment of C. elegans with ethanol elevated the sodh-1 expression and ROS accumulation while repressing a series of immunity genes that were also repressed during fungal infection. Mutation of sodh-1 in C. elegans blocked ROS accumulation and increased the nematode’s susceptibility to fungal infection. Our study revealed a new recognition and antifungal mechanism in C. elegans . The novel mechanism of ethanol-mediated interaction between the fungus and nematode provides new insights into fungal pathogenesis and for developing alternative biocontrol of pathogenic nematodes by nematophagous fungi. IMPORTANCE Nematodes are among the most abundant animals on our planet. Many of them are parasites in animals and plants and cause human and animal health problems as well as agricultural losses. Studying the interaction of nematodes and their microbial pathogens is of great importance for the biocontrol of animal and plant parasitic nematodes. In this study, we found that the model nematode Caenorhabditis elegans can recognize its fungal pathogen, the nematophagous fungus Purpureocillium lavendulum , through fungal-produced ethanol. Then the nematode elevated the reactive oxygen species production in the gut to inhibit fungal growth in an ethanol dehydrogenase-dependent manner. With this mechanism, novel biocontrol strategies may be developed targeting the ethanol receptor or metabolic pathway of nematodes. Meanwhile, as a volatile organic compound, ethanol should be taken seriously as a vector molecule in the microbial–host interaction in nature.