The Detection Of Mutation On Mitochondrial DNA And Clinical Analysis In Leber Hereditary Optic Neuropathy--A Pedigree Of 18 Person

Leber hereditary optic neuropathy is an inherited disease mainly correlated with papillomacular bundle and resulting in degeneration of the optic nerve. The disease is inherited through materal transmission. It characterized by acute or subacute loss of central vision and optic atrophy.The mean age of onset is between age 18 and 30.The number of male patients is much more than female patients.Recently,mitochondrial DNA mutation is found to be responsible for Leber hereditary optic neuropathy.The most frequent three mutations are 3460/ ND1(G→A),11778/ ND4(G→A) and 14484/ ND 6(T→C),considered as primary mutation.Those three mutations will cause more than 95% of LHON cases totally.G11778A,however,is the most common mutation in LHON(50-52%).In this study,polymerase chain reaction(PCR)- restriction endonuclease analysis is used to detect the three frequent mitochondrial DNA mutations in a pedigree associated with Leber hereditary optic neuropathy.The purpose of this study is to investigate whether the mitochondrial DNA mutation exists and to prove the diagnosis of this pedigree is correct.We collect the clinical information in the members of the family.Blood samples were gathered from the members of this pedigree.The total DNA including mitochondrial DNA were extracted from leucocyte.Three pairs of primers were designed for the three nucleotide positions(3460,11778,14484) by Pcrdesn soften system.The samples were amplified by PCR and the PCR products were digested with the restriction endonuclease of HinI 1,SfaN 1 and Sau3A 1 respectively.Finally,we analyse the result on the 2% gel and find mitochondrial DNA mutation at nucleotide position 11778 of mitochondrial DNA in some members of this pedigree.In conclusion,most of the members of this pedigree were suffered from Leber hereditary optic neuropathy . Mitochondrial DNA mutation at nucleotide position 11778 caused Leber hereditary optic neuropathy in this family.We found that,in this study,all the information we have to support the diagnosis of LHON.Firstly,the disease development of this pedigree is consistent with the characteristics of materal transimission.Secondly,the clinical behavior is identical with Leber hereditary optic neuropathy.Thirdly, mitochondrial DNA mutation at nucleotide position 11778 in this pedigree was found in the study.Finally, a single mitochondrial DNA mutation can cause Leber hereditary optic neuropathy. By the work we did,it shows that polymerase chain reaction(PCR) can be used for the detection of the mitochondrial DNA mutation.Mitochondrial DNA mutation plays a role in Leber hereditary optic neuropathy.It provides the theory basis and technological method for the mutation analysis.It provides the foundation for the diagnosis and the differential diagnosis of neuropapillitis,family optic neuropathy and suspected LHON cases.It also provides theoretical basis and studying direction for treatment with Leber hereditary optic neuropathy.We can also evaluate the visual prognosis of the patients in pedigrees according to these mutations of mitochondrial DNA.