| Leber's hereditary optic nuropathy (LHON) is a maternally inherited disease that causes bilateral central visual loss, predominantly in young men. The basic pathological change of LHON mainly happened to the micrangium of optic papilla. Until 1988, the theory of mitochondrial mutation has excited most of researcher's attention after Wallace found that there is a mutation point in mitochondrial DNA in the patients of LHON. Currently, three mutation points, 3460, 11778, 14484, in mtDNA of human beings are thought as primary mutation of LHON, and can be detected in 90% patients in LHON.LHON takes on obviously hereditary. Though the incidence of LHON is relatively low worldwide, it happens to most young adults and can affect seriously the life quality of LHON. To clarify the hereditary rule, pathogenic or pathogenesis of LHON is not only benefit of early found, prevent and therapy of LHON, but also have important significance to basic and clinical study of other optic neuropathy. Though similar reports are hot points overseas, it is only in the early stage of LHON and systemic research are needed in our country.The aim of this study is to find economical methods for rapid diagnostic and antepartum consultation of LHON through PCR-SSCP and DNA sequencing. At the same time, the relationship between oxidative phosphorylation and LHON is also discussed in order to know the pathogenesis of LHON.vThe contents and results of this study is listed as follows:I. Detection of the primary mutation of LHONMitochondrial DNA was abstracted from the leukocyte of venous blood gained from probands and their matritineal relatives. Using the three primers which designed to 3460, 11778 and 14484 of mtDNA, we got three DAN fragment. Restriction endonuclease analysis, SSCP and DNA sequencing were applied to detected whether there are the three point mutations. These are the results:1. In all the patients who have been clinical diagnosed as LHON, there are 78 patients who have the G11778A mutation, the ratio is 95.2%, which there are 61 men and 12 women. There is only one patient who endured G3460A mutation, and the ratio is 1.2%. And there are four patients have T14484C mutation, the ratio is 4.8%. Additionally, 9 of 14 sporidic LHON patients are found have the G11778A mutation, which the ratio is 64.3%. The normal controls have none of above mutation points.2. For G11778A, there are 73 patients are not found the endonuclease site of Sfa NI while the matritineal relatives and normal controls all have. The mobility in SSCP is significant difference in LHON compared to those who are not LHON. The sequencing of PCR products analyzing suggest that there is G-A mutation on the site of 11778.3. In this study, one patients of LHON are found have no endonuclease site of Bsa HI while others have. The mobility in SSCP is significant difference in LHON compared to those who are not LHON. The sequencing of PCR products analyzing suggest that there is G-A mutation on the site of 3460.4. In this study, four patients who have T14484C mutation are found through the endonuclease, SSCP and sequencing analysis.II. Relationship between oxidative phosphorylation and LHONIn order to clarify the relationship between oxidative phosphorylation and LHON, 20 patients of LHON who have G11778A mutation, 20 matritineal relatives of the LHON patients and 20 normal controls are selected and the activity of complex I are detected. The results suggested that the activity of complex I in the platelet of LHON was significant decreasing compared to that of the normal and the matritineal relatives.The conclusion from this study can be draw according to this study:1. It is the first reports that there is genalogy of LHON in which the patients of can be tested have G3460A mutation. Though the G11778A point mutation in mtDNA is normal, there still exist G3460A and T14484C mustational patients.2. Oxidative phosphorylation in mitochondria is the most important energy source to our body. In our study, we found that the activity of complex I in mit...
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