七个眼皮肤白化病I型家系的早期产前诊断

Early prenatal genetic diagnosis of oculocutaneous albinism type I in seven families

目的探讨酪氨酸酶基因（tyrosinase，TYR）检测用于眼皮肤白化病I型（0culocutaneous albinism type I，OCAl）产前诊断的可行性。方法采用聚合酶链反应扩增与DNA直接测序技术对7个OCAl家系的先证者及其父母的TYR基因进行序列分析。在确定先证者或携带者的基因型后，对高危胎儿取胎盘绒毛进行产前诊断。结果7个家系中均检出了TYR基因的复合杂合突变，包括R76Q、C．232insGGG、R116X、R278X、R299H、c．929—930insC、IV$2-1ldelTT、Q399X和W400L共9种，其中R76Q和Q399X为尚未报道的突变。对7个家庭的胎儿行产前诊断，1名胎儿携带与先证者相同的双突变，行引产术；2名胎儿未携带TYR基因突变，4名为突变携带者。6个家庭均选择继续妊娠，随访至出生后新生儿表型均无异常。结论应用基因测序技术对TYR基因行突变分析可有效减少生育OCA1患儿的风险。

Objective To evaluate the feasibility of genetic analysis of tyrosinase gene （TYR） in oculocutaneous albinism type I （OCA1）. Mutation analysis and prenatal genetic diagnosis of TYR gene for seven pedigrees with OCA1 were performed. Methods PCR was used to amplify the exons, exon-intron boundaries and promoter of the TYR gene in the probands and/or their parents. The products were further analyzed by direct sequencing. Prenatal genetic diagnoses were performed by chorionic villus sampling after the genotypes of the probands or their parents were determined. Results Compound heterozygous mutations were detected in all pedigrees, which included 9 mutations, namely R76Q, c. 232insGGG, Rll6X, R278X, R299H, c. 929-930insC, IVS2-11delTT, Q399X and W400L. Among these, R76Q and Q399X were identified for the first time. Seven families have requested prenatal diagnoses. One fetus was detected with double mutations of TYR gene, and the parents have decided to have therapeutic abortion. Two fetuses did not carry the mutations identified in the probands, whilst other four fetuses were carriers of heterozygous mutations. Six families decided to carry on with the pregnancies. And the neonates did not show any symptoms of OCA after birth. Conclusion Direct sequencing of the TYR gene is helpful for genetic counseling, prenatal diagnosis and carriers screening of OCA1.