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Temperature-sensitive tyrosinase associated with peripheral pigmentation in oculocutaneous albinism
R A King1, D Townsend, W Oetting
1Department of Medicine, University of Minnesota, Minneapolis 55455.
The Journal of Clinical Investigation
|March 1, 1991
Summary
This study identifies a novel form of oculocutaneous albinism (OCA) caused by a temperature-sensitive tyrosinase enzyme. This genetic mutation results in hair color varying with body temperature, a first in human albinism research.
Area of Science:
- Genetics
- Biochemistry
- Dermatology
Background:
- Autosomal recessive oculocutaneous albinism (OCA) typically involves tyrosinase dysfunction, leading to reduced melanin in skin and eyes.
- Existing OCA types are linked to distinct mutant alleles at the tyrosinase locus, each causing low or absent enzyme activity across tissues.
Observation:
- A proband presented with hair color varying by temperature: white in warmer areas (scalp) and darker in cooler areas (extremities).
- Melanocyte and melanosome structures were observed to be normal in the affected individual.
Findings:
- A new type of OCA was identified, resulting from a tyrosinase allele that produces a temperature-sensitive enzyme.
- Quantitative assays revealed a loss of tyrosinase (dopa oxidase) activity above 35-37°C.
- Reduced plasma pheomelanin and urine eumelanin intermediates correlated with hair melanin levels.
Implications:
- This discovery marks the first reported instance of a temperature-sensitive tyrosinase mutation in humans.
- The findings provide a human parallel to temperature-sensitive mutations observed in animal models, such as the Siamese cat and Himalayan mouse.
- Understanding temperature sensitivity in enzyme function offers new insights into genetic disorders and pigment biology.
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