Background The mutation of the tyrosinase （TYR） gene results in oculocutaneous albinism type 1 （OCA1）, an autosomal recessive genetic disorder. OCA1 is the most common type of OCA in the Chinese population. Hence,...Background The mutation of the tyrosinase （TYR） gene results in oculocutaneous albinism type 1 （OCA1）, an autosomal recessive genetic disorder. OCA1 is the most common type of OCA in the Chinese population. Hence, the TYR gene was tested in this study. We also delineated the genetic analysis of OCA1 in a Chinese family. Methods Genomic DNA was isolated from the blood leukocytes of a proband and his family. Mutational analysis at the TYR locus by DNA sequencing was used to screen five exons, including the intron/exon junctions. A pedigree chart was drawn and the fundus of the eyes of the proband was also examined. Results A novel missense mutation p.1151S on exon 1, and homozygous TYR mutant alleles were identified in the proband. None of the mutants was identified among the 100 normal control subjects. Genetic analysis of the proband＇s wife showed normal alleles in the TYR gene. Thus, the fetus was predicated a carrier of OCA1 with a normal appearance. Conclusion This study provided new information about a novel mutation, p.1151S, in the TYR gene in a Chinese family with OCAI. Further investigation of the proband would be helpful to determine the effects of this mutation on TYR activity.展开更多
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...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。展开更多
基金This study was supported in part by grants from the Natural Science Foundation of Beijing （No. 7092040）, the Capital Medical Development Foundation （No. 2007-3111）, and the National Natural Science Foundation of China （No. 31071252）.
文摘Background The mutation of the tyrosinase （TYR） gene results in oculocutaneous albinism type 1 （OCA1）, an autosomal recessive genetic disorder. OCA1 is the most common type of OCA in the Chinese population. Hence, the TYR gene was tested in this study. We also delineated the genetic analysis of OCA1 in a Chinese family. Methods Genomic DNA was isolated from the blood leukocytes of a proband and his family. Mutational analysis at the TYR locus by DNA sequencing was used to screen five exons, including the intron/exon junctions. A pedigree chart was drawn and the fundus of the eyes of the proband was also examined. Results A novel missense mutation p.1151S on exon 1, and homozygous TYR mutant alleles were identified in the proband. None of the mutants was identified among the 100 normal control subjects. Genetic analysis of the proband＇s wife showed normal alleles in the TYR gene. Thus, the fetus was predicated a carrier of OCA1 with a normal appearance. Conclusion This study provided new information about a novel mutation, p.1151S, in the TYR gene in a Chinese family with OCAI. Further investigation of the proband would be helpful to determine the effects of this mutation on TYR activity.
文摘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。
