Those genes include agouti signalling protein (ASIP), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), oculocutaneous albinism II (OCA2), various solute carrier genes and transporters.
The implication of the tyrosinase assay results in light of the phenotype and the possible location of the pigment block in these forms of OCA are discussed.
Here, we describe the analysis of the HPS1 gene in 24 Japanese OCA patients who lacked mutations in the four genes known to cause OCA (TYR/OCA1, P/OCA2, TYRP1/OCA3, and MATP/OCA4), and the identification of eight different HPS1 mutations in ten of these patients, four of which were novel (W583X, L668P, 532insC, 1691delA).
Sequence analysis of the tyrosinase (TYR) coding region from one albino rhesus monkey (Macaca mulatta) family revealed that the two monkeys with phenotype similar to human TYR-negative oculocutaneous albinism (OCA) were homozygous for a missense mutation (S184TER) in exon 1 at codon 184.
This mutation, which results in a proline----leucine substitution at codon 81 of the tyrosinase polypeptide (EC 1.14.18.1), was observed in 20% (6 of 30) of oculocutaneous albinism alleles from independent probands, but it was not observed in any normal individuals.
Three PUAs (p.P152H and p.W272X of TYR, p.A486T of SLC24A5) identified in the OCA probands did not co-transmit with known pathological alleles and thus gave rise to unaffected fetuses.
The Hermansky-Pudlak Syndrome, a "tyrosinase positive' form of oculocutaneous albinism, is a triad comprising albinism, a hemorrhagic diathesis and ceroid-lipofuscin storage.
Oculocutaneous albinism (OCA) is a group of autosomal recessive disorders characterized by reduced melanin that are caused by mutations in the gene encoding tyrosinase (TYR), which is the rate-limiting enzyme in the production of the pigment melanin.
Genetic analysis was subsequently conducted, and the results revealed the p. (Arg778Leu) mutation in 1 allele and the p. (Asn1270Ser) mutation in the other allele of the ATP7B gene, confirming the diagnosis of WD; the p. (D456fs) mutation in 1 allele and the p. (R299H) mutation in the other allele of the TYR gene, confirming the diagnosis of OCA.
We identified five different mutations in the TYR gene in 4 patients with severe OCA and in 2 patients with mild OCA, but found no mutations in the 6 patients with mild OCA phenotypes.
TYR gene mutations represent a relevant cause of oculocutaneous albinism in Italy, whereas mutations in P present a lower frequency than that found in other populations.