Eye Fissure Narrow Syndrome, Atopic Dermatitis And Other Skin Diseases, Gene Mutation Studies

Genetic disease are the diseases due to the changes in genetic materials. These changes can be at chromosome level, or molecular level. There are four different types of genetic disorders: 1.chromosome disorders; 2.single gene; 3.multifactorial; and 4.mitochondrial.By 2003, the completion of Human Genome Project led genetics to the genomics period, which also opened up a new century to the research of hereditary disease. At present there are many kinds of diseases related to genetics can do harm to people's health and the quality of life. This master's thesis is mainly about the research of FOXL2 mutations in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndrome and FLG gene polymorphisms and atopic dermatitis; COL7A1 gene mutations and gystrophic epidermolysis bullosa and LOR gene mutations in progressive symmetric erythrokeratodermia. We explored the pathogenesy of these diseases in the aspect of molecular genetics and then the research can provide evidence for the prenatal diagnosis, prevention and genetic counseling of these diseases.1. FOXL2 mutations in Chinese patients with blepharophimosis-ptosis-epicanthus inversus syndromeBackground: Classic blepharophimosis syndrome (BPES) is a complex eyelidmalformation invariably characterized by four major features: blepharophimosis, ptosis, epicanthus inversus, and telecanthus. Two types of blepharophimosis syndrome have been described: BPES type I includes the four major features and female infertility caused by premature ovarian failure (POF); BPES type II includes only the four major features. FOXL2 is the only gene currently known to be associated with BPES.Objective: To identify mutations in FOXL2 of Chinese patients with BPES. Methods: Extract genomic DNA from the BPES patient, PCR and DNA sequencing.Results: The delete mutation 17bp (1081-1097del ) was identified in family A. Theunknown insert mutation was identified in family B and C.Conclusion: This mutation 17bp (1081-1097del) is the first report in Chinese patients, our results expand the spectrum of FOXL2 mutations.2.1 FLG Gene Polymorphisms and Atopic DermatitisBackground: Filaggrin is a key protein involved in skin barrier function. Recently,mutations in the filaggrin gene, FLG, were identified in European families with ichtyosis vulgaris(IV) and shown to be an important predisposing factor for atopic dermatitis(AD).Objective: To study the role of FLG polymorphisms in AD in ChineseMethods: The known filaggrin polymorphisms were studied by genotying and new mutations identified by DNA sequencing.Results: The European-specific polymorphisms R501X and 2282del4 were absent in 166Chinese individuals(22 AD patients and 144 normal healthy control). The Japan-unique mutations 3321delA and S2554X, S2554X were also absent in 166 Chinese individuals(22 AD patients and 144 normal healthy control); 3321delA were identified in 3 patients with AD(13.64%) , 9 were identified in 144 unrelated Chinese nonatopic and nonichthyotic controls(6.25%). This is the first study of FLG mutation in a Chinese population.Conclusion: Our data indicate that FLG mutations in Chinese are unique from those foundin European-origin populations.2.2COL7A1 Gene Polymorphisms and Dystrophic epidermolysis bullosa (DEB)Background: The only gene known to be associated with DEB is COL7A1.COL7A1 mutations centered in exons 73-75 in Oriental on the basis of the literatures. We suppose that mutation hotspot probably located inexons 73-75 of COL7A1 in Oriental.Objective: To identify gene mutation of 2 Dystrophic epidermolysis bullosa.Methods: The polymerase chain reaction(PCR) and DNA sequencing. Results: No mutation is identified in exons 73-75 of COL7A1 in our 2 RDEB patients.Conclusion: Sequencing of the entire coding region is necessary to identify both mutations in individuals with RDEB because the mutation is varies in the different family.2.3 Single Case Detection of LOR Gene Mutation of ProgressiveSymmetric Erythrokeratodermia(PSEK)Objective: To study the mutation of the loricrin gene in PSEK patient.Methods: Extract genomic DNA from the PSEK patient, PCR and sequencing the wholecoding region of the loricrin gene.Results: No disease causing mutations were detected in the loricrin gene by directsequencing.Conclusion: Our study provides the evidence for genetic heterogeneity of PSEK andloricrin gene might not a causing factor for PSEK.