Genetic Analysis Of Nonsyndromic Oculocutaneous Albinism In Chinese Families And Prenatal Genetic Diagnosis Of Abinism

Objective 1) To establish the relative prevalence of different genotypes and gene mutations of nonsyndromic OCA among Chinese families.2) To investigate the values of fetoscopy and gene mutation detection in prenatal diagnosis of OCA.Methods 1) We collected 83 samples of genomic DNA,including the proband, parents and fetus,from 26 non-consanguineous OCA families for prenatal genetic counseling.We also collected the clinical phenotypes of the probands.Mutations of the TYR,P,MATP and TYRP1 genes among family members were extensively screened by using PCR-SSCP coupled with direct sequencing.The frequencies of mutational alleles as well as correlations between genotype and phenotype of the probands were analyzed. 2) Prenatal diagnosis of OCA were performed among 14 families by using fetoscopy and genetic analysis.The advantages and disadvantages of the two different prenatal diagnostic methods were evaluated.Results 1) 47 out of 52(90%) allelic mutations were detected.Among the 26 Chinese families,72%(19/26) had OCA1,8%(2/26) had OCA2,none had OCA3, 16%(4/26) had OCA4,and 4%(1/26) had no detectable pathologic mutations in any of the genes studied.We identified 23 different TYR mutations in 19 families,5 different P mutations in 2 families,and 6 different MATP mutations in 4 families.Among 19 OCA1 families,P930insC and R299H were present in 7 out of 38 alleles and 6 out or 38 alleles respectively,which were the most frequent mutations in Chinese TYR gene. We also identified 8 novel TYR gene mutations(C100P,C100T,R212T,T235G,R299C, G506L,1348 insGG,â…£S2-17insAC),3 novel P gene mutations(T450L,A455G, L727P) and 5 novel MATP mutations(G110A,L151S,A160G,Y266X,1-6del gtggccatgg ) which have not been reported in the literatures.84%of OCA1A and only 29%of OCA2 clinically diagnosed were confirmed by the molecular results.The clinical appearance overlaps between different OCA types.2) In 14 families for prenatal diagnosis of OCA,fetoscopy showed 92%confirm rate while genetic analysis showed 100%confirm rate. Conclusions Genetic analysis in 26 Chinese nonsyndromic albinism families showed that OCA1 may be the major type of Chinese OCA.P930insC and R299H may be the most frequent mutational alleles.Prenatal diagnosis are possible when the disease causing mutations have been identified in the family.Compared with traditional fetoscopy diagnosis,prenatal genetic diagnosis is more accurate.