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
Tyrosinase is encoded by the Tyr (c or albino) locus and is the key enzyme in pigment biosynthesis. Loss of function of this enzyme caused by gene mutation results in albinism. Most cases of albinism are caused by mis...Tyrosinase is encoded by the Tyr (c or albino) locus and is the key enzyme in pigment biosynthesis. Loss of function of this enzyme caused by gene mutation results in albinism. Most cases of albinism are caused by missense mutations of tyrosinase. Albino mutations in Tyr have been identified in various animals, including human, mouse, rat, rabbit, cattle, cat, and ferret, but not in gerbil. We created two new gerbil strains: MON/Num/a (inbred agouti phenotype) and MON/Num/c (albino phenotype). Here, we report that four nucleotide substitutions in the Tyr gene caused two missense mutations in amino acids in the albino gerbil: a G-to-A mutation at position 204 in exon 1 caused R77H, and A-to-G at position 1392 and G-to-T at position 1393 in exon 5 caused Q473R. The substitution at position 1408 in exon 5 was silent. These missense mutations are conserved in all albino phenotypes we tested. Therefore, we suggest that these mutations are responsible for albinism in gerbil.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Tyrosinase is encoded by the Tyr (c or albino) locus and is the key enzyme in pigment biosynthesis. Loss of function of this enzyme caused by gene mutation results in albinism. Most cases of albinism are caused by missense mutations of tyrosinase. Albino mutations in Tyr have been identified in various animals, including human, mouse, rat, rabbit, cattle, cat, and ferret, but not in gerbil. We created two new gerbil strains: MON/Num/a (inbred agouti phenotype) and MON/Num/c (albino phenotype). Here, we report that four nucleotide substitutions in the Tyr gene caused two missense mutations in amino acids in the albino gerbil: a G-to-A mutation at position 204 in exon 1 caused R77H, and A-to-G at position 1392 and G-to-T at position 1393 in exon 5 caused Q473R. The substitution at position 1408 in exon 5 was silent. These missense mutations are conserved in all albino phenotypes we tested. Therefore, we suggest that these mutations are responsible for albinism in gerbil.
