Dissertation > Medicine, health > Ophthalmology > Retina and optic nerve diseases > Retinal disease

The Study of Mutation in the CRX Gene Associated with Late-onset Genetic Retinitis Pigmentosa (RP)

Author LiuQing
Tutor MaXiang
School Dalian Medical University
Course Ophthalmology
Keywords late-onset genetic Retinitis pigmentosa CRXgene gene mutation
CLC R774.1
Type Master's thesis
Year 2011
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Background: Retinitis pigmentosa( RP)is a progressive inherited retinal diseases, which can damage the photoreceptor cells, and its worldwide incidence rate is about 1 / 3500, China’s incidence rate is about 1 / 3784, although the exact cause is unknown, and No obvious predisposing factors, but the molecular biology studies from worldwide have shown that the disease is a serious genetic disease, with familial aggregation characteristics. The typical mode of inheritance are: autosomal dominant (accounting for 20%), autosomal recessive (accounting for 37%), X chromosome-linked recessive inheritance (5%), the performance of a double handful of genetic mutations and mitochondrial Genetic, the other, there are still 39% -50% of the cases showed distribute, or naturally occurring cases. At abroad have been successfully cloned 40 kinds of mutant genes, including the CRX gene mutation: Arg41Trp ,in the coding sequence of the CRX gene,that has been found in the United States, Germany, Japan, Finland and other countries, while China has not been reported.CRX gene (as the vertebrae - rod homeobox gene) is a photoreceptor-specific transcription factor, in the human genome 19q13. 3, containing 3 exons, as homologous Gene of the OTX (correct homologous gene family) ,and express the receptor-protein of photoreceptors, controlling RHO gene (the most common genetic cause dominant RP) of its initial activity, CRX gene mutation can lead to functional decline in the transcription of proteins, causing late-onset retinal pigment Degeneration, may also cause congenital amaurosis, autosomal dominant inheritance of the cone rod dystrophy and other clinical diseases.Purpose :The experiment was carried out by analyzing CRX gene in a late-onset retinitis pigmentosa pedigree in China’s southeast of the Liaoning Province,to clarify whether its incidence was related with CRX mutation.Methods: Collection patients from Ophthalmology clinic of the first Affiliated Hospital of Dalian Medical University patients with primary retinitis pigmentosa (including familial and sporadic), by history, age at onset, clinical manifestations, associated equipment inspection screen to choose delayed retinitis pigmentosa patients in one Pedigree, A total of 22 family members, female 10, male 12, the onset accounted for nine members, of the other fellow are the normal family and spouses, the whole age range is 15 to 78 years old. Each group signed an informed consent form, collected peripheral blood 2ml from everyone, extract the white blood cell DNA, use the ultraviolet light detect the concentration and purity of DNA;Use Primer-5 software design three pairs of primers for the study of the three exons of CRX including the coding region, and then apply the polymerase chain reaction (PCR) to amplify the purpose domain of CRX gene , then PCR products were detected by agarose gel electrophoresis, the sequencing was comparised with the normal human CRX gene sequence,to clarify whether the amplified products is the purpose gene fragments ,after the PCR products were purified ,by direct sequencing, to identify if the CRX gene in the the pedigree have mutations generated. Investigate if CRX gene mutation exists in the patients with late-onset RP of the chinese people.Results: In this study, PCR amplification of the three exons and coding region of CRX gene through direct sequencing ,sequencing fragments obtained, failed to find any exons or the adjacent splice mutation related with the study of the disease. Tip of there is no significant correlation between CRX gene and delayed retinitis pigmentosa in this pedigree.Conclusion: There are no significant correlation between CRX gene and late-onset retinitis pigmentosa in this pedigree in the southeast region of Liaoning province. In the view of molecular genetics, there is considerable genetic heterogeneity in retinitis pigmentosa (RP), suggesting that the same gene in different countries or ethnic groups, with differences in their pathogenicity.

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