Study On OCA Gene Mutation And Its Pathogenic Mechanism

Oculocutaneous albinism(OCA) is a group of autosomal recessive disorders which ischaracterized by absent biosynthesis of melanin pigment in melanocytes of the eyes, skin, andhair follicle. With high locus heterogenetity and allelic heterogeneity, OCA is the most commonform of albinism. Based on clinical and molecular criteria, four types of OCA(OCA1-4) havebeen described up to now. They are associated with mutations in the tyrosinase gene, P proteingene, tyrosinase-related protein gene(TYRP1) and membrane associated transporter gene(MATP)respectively.In order to explore the gene mutations spectrum of OCA in China and build up suitablegene diagnosis methods of OCA for China, by means of direct DNA sequencing we analyzed theTYR gene, P gene, TYRP1gene and MATP gene of24OCA patients from different provinces inChina from March2010to March2012. Eleven of them were genetically diagnosed as OCAl,eight as OCA2and three as OCA3. Two of them were diagnosed as OCAl and OCA2by clinicalphenotype but weren’t detected mutations in the four genes.We detected13different mutations in the TYR gene(R299H, W400L, R239W, G291E,R217P, R116X, R278X,929insC, IVS4+3A>T,232insGGG,559ins25bp,546-549delTG and807delCTC),11different mutations in the P gene(L727P, R419W, S788L, L295P, R555V,T404M, R572C, G420X, IVS11+1G>A, IVS7-3C>G, V443I, Q269E and L611P),4differentmutations in the MATP gene (G349R, P419L, D160H and M3deficiency). After browsing theinternational literature and the database of international albinism center, it is known that546-549delTG、807~812delCTC and G291E have not been reported as novel TYR genemutations, that S788L、L295P、R555V、R572C、G420X and Q269E have not been reported asnovel P gene mutations. By means of structural predictions of the protein and restrictionendonuclease analysis, the pathologic effects of the novel murations were analyzed. The resultsindicated that these novel nuclear changes were probably pathologic ones causing OCAphenotype.In conclusion, We analyzed24cases of OCA patients, and identified5novel pathologicmutations of TYR gene,7novel pathologic mutations of P gene and2novel pathologic mutations of MATP gene. The results of this work enriched the gene mutations of human OCA.To some extent, it may be the initial groundwork to build up gene diagnosis methods fordifferent types of OCA in China.