PubMed:2120217 JSONTXT 29 Projects

Molecular basis of tyrosinase-negative oculocutaneous albinism. A single base mutation in the tyrosinase gene causing arginine to glutamine substitution at position 59. Tyrosinase-negative oculocutaneous albinism (OCA) is one of classical inborn errors of metabolism, characterized by a complete lack of melanin pigments in the eyes and skin. We have isolated and characterized the tyrosinase gene of one child (F. S.) affected with tyrosinase-negative OCA. Sequence analysis reveals a single-base mutation in the exon 1 (a G to A transition at nucleotide residue 312), causing the Arg (CGG) to Gln (CAG) substitution at position 59. This base change eliminates one MspI site and creates a new BstNI site in the patient's exon 1, which is invaluable for screening other OCA patients and heterozygote carriers for this mutation. We are thus able to confirm that the patient F. S. is homozygous for this OCA allele. The family members of the patient F. S. are phenotypically normal, but are shown to be heterozygote carriers. Transfection of the mutant gene fails to give rise to detectable tyrosinase activity in transient expression assays, suggesting that the mutation affects the stability or the catalytic activity of the enzyme. We therefore propose that the albino phenotype of the patient F. S. is a consequence of the Arg to Gln substitution at position 59 caused by a point mutation in the tyrosinase gene.