A Research On The Relativity Between Clinical Characteristics Of Leber Hereditary Optic Neuropathy And Genetic Mutation

BackgroundLeber hereditary optic neuropathy is a mitochondrial ophthalmopathy which is doing severe harm to youngsters, characterized clinically by acute or subacute impairment of binoculus central vision generally without eyeball pain or sore under press, revealing central scotoma and paracentral scotoma under examination of visual field. As manifested by epidemiological investigation, the attack rate of LHON around the world is1/31000, and1/39000and1/50000in Holland and Finnish respectively. At present, it is received that there are three primarily pathogenic points of LHON, respectively located at point3460in ND1area, point14484in ND6area and point11778in ND4area, and95%of LHON is caused by one of the three above-mentioned primarily pathogenic mutable points, and the mutation rate of which is92.9%,1.4%and5.7%respectively in our country. In China, G11778Amutation is most frequently, T14484C mutation is less and G3460A is rarely. LHON is easily missed or misdiagnosed for its being always sporadic case and the diversity as for its onset and course of disease, so by screening LHON patients through gene diagnosis, mutation points can be quickly and accurately located, which will play an active role in protection and treatment of LHON. ObjectiveTo probe into the Leber hereditary optic neuropathy (LHON) patients’mtDNA mutation types and hereditary character in the Central Plains, and to screen the new secondary mutations of Chinese LHON patients.MethodsFirstly undertake ophthalmologic examination and MRI examination on189suspected LHON cases, included in three family constellations. And carry out mtDNA detection on the point G11778A, G3460A and T14484C of189patients with suspected LHON clinical symptom by the combined DNA sequencing methods of allele-specific PCR (AS-PCR), polymerase chain reaction-fragment length polymorphism (PCR-RFLP) and polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). Then process an entirely genomic sequencing on the mitochondria of the suspect patients who lack of three primary mutable points, and search the other secondary mutations relating the disease.Results1、Among the189suspected LHON patients,86cases are finally diagnosed as primary mutation located at one of the three pathopoiesis points G11778A, G3460A�'�T14484C of the central plains, LHON patients with G11778A sites still mainly mutations, followed by T14484C, G3460A the most rare mutations.2、Among the86primary mutation cases, there are6point3460mutation cases, accounting7%;66point11778mutation cases, accounting77%;14point14484mutation cases, accounting16%.3、Among14point14484mutation cases,3cases are only14484primary mutation, accounting22.2%, all male;5cases have14484mutation and14502mutation, accounting33.3%,1male and2female;4cases combination have14484mutation and14470mutation, accounting33.3%,2male and1female;2cases have14484mutation and14569mutation, accounting11.1%.4、Through an entirely genomic sequencing on the mitochondria, these mutation points are found, A2706G, A1438G, T2115C, G3538T, G3834A, C4262A, C4275G, C7028T, G8392A, A10485G and C10719T, some of which exist in healthy people.Conclusion1、in the Central Plains, LHON is still mainly caused by point G11778A mutation, then by T14484C mutation and seldom by G3460A mutation.2、Among the point T14484C mutation cases, there are only14484primary mutation, combination of point14484primary mutation and point14502mutation, combination of point14484mutation and point14569mutation as well as combination of point14484mutation and point14470mutation.ND6area is one of the hot spots in research on DNA mutation.3、Entirely genome sequencing on the mitochondria shows that some new secondary mutation points may generate cooperative effect in primary situs pathopoiesis, while how it works needs further research.