ABSTRACT
Oculocutaneous albinism (OCA) is a group of inherited disorders of the melanin synthesizing system, and these are characterized by hypopigmentation of the hair, skin and eyes, with a normal number of melanocytes. The defect of melanin biosynthesis is caused by genetic mutation of such enzymes as tyrosinase (TYR), and tyrosinase-related protein (TYRP), which affect tyrosine convert to melanin pigment. There are at least four types of OCA from OCA1 to OCA4. The different types of OCA are caused by mutations in different genes. The most severe form, OCA1A, is distinguishable from other forms owing to a complete lack of melanin pigment throughout the patient's whole life. But among other types, except OCA1A, it is hard to identify the correct type according to only the clinical findings because their clinical phenotypes usually overlap. Therefore, molecular study is a useful tool for the typing and diagnosis of OCA. We experienced a case of a 10-month-old male toddler who has pale skin, straw-colored hair, nystagmus and visible choroidal vessels. Under the clinical impression of OCA, the correct subtyping was made on the basis of genetic analysis of the chromosomes and we found a new TYR gene frame-shift mutation.
Subject(s)
Humans , Infant , Male , Albinism, Oculocutaneous , Choroid , Eye , Hair , Hypopigmentation , Melanins , Melanocytes , Monophenol Monooxygenase , Phenotype , Skin , TyrosineABSTRACT
The gene for tyrosinase has been mapped to the long arm of chromosome 11 at 11q14-21. The gene is at least 50Kb in length and its coding region is divided into five exons. Until now several mutations of the tyrosinase gene have been identifed in patient with typical oculocutaneous albinism (OCA) who are responsible for tyrosinase negative OCA. It may be possible to determine the types of OCA by measuring the hairbulb tyrosinase activity. Hairbulb tyrosinase activity was examined in a Korean albino to determine the type of OCA. And also tyrosinase assay was carried out in normally pigmented individuals and all members of a Korean albino's family to examine the tyrosinase activities. Five exons of tyrosinase gene from a Korean albino were amplified by polymerase chain reaction. Each amplified exon segments were independently subcloned and DNA sequences of clones were determined. The results obtained were as follows : 1. A Korean albino had no measurable hairbulb tyrosinase activity and was identified as type IA (tyrosinase negative) oculocutaneous albinism. 2. Normally pigmented individuals had different ranges of hairbulb tyrosinase activity. 3. A Korean albino had two single base insertions within exon V (between 337bp and 338bp, 353bp and 354bp) of tyrosinase gene. These insertional mutations might disrupt tyrosinase function and were associated with a total lack of melanin biosynthesis.
Subject(s)
Humans , Albinism , Albinism, Oculocutaneous , Arm , Base Sequence , Chromosomes, Human, Pair 11 , Clinical Coding , Clone Cells , Exons , Melanins , Monophenol Monooxygenase , Polymerase Chain ReactionABSTRACT
BACKGOUND: Because heterogeneity of the human tyrosinase gene has been reported, it is of vital significance to know the correct nucleotide sequence of tyrosinase in Koreans in order to study the molecular basis of oculocutaneous albinism. OBJECTIVE: This study was done to analyze the nucleotide sequence of tyrosinase gene in Koreans. METHODS: All exons were amplified from genomic DNAs and sequenced directly from three healthy Koreans. RESULTS: The nucleotide sequence of the tyrosinase gene in Koreans encode 511 amino acids with a molecular weight of 58,000. CONCLUSION: The nucleotide sequence of coding region is the same with that of pHTrl(Shibahara et al. Tohoku J Exp Med 156: 403-414, 1988). As we couldn't observe any polymorphisms in Koreans these results suggested the homogeneity of Korean people.