However, the complete deglycosylation of asparagine residues in vitro, including the residue in position 371, interrupts tyrosinase function, which is consistent with a melanin loss in oculocutaneous albinism type 1 (OCA1) patients.
Two subtypes of OCA1 have been described: severe OCA1A with complete absence of tyrosinase activity and less severe OCA1B with residual tyrosinase activity.
Functional characterization of nonsynonymous tyrosinase variants in patients with OCA1 reported in the Albinism Database, dbSNP and the published literature, and an attempt to correlate them with reported and predicted phenotypes.
This advance allows for the structure - function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1.
We hypothesized that increasing plasma tyrosine concentrations using nitisinone, an FDA-approved inhibitor of tyrosine degradation, could stabilize tyrosinase and improve pigmentation in individuals with OCA1.
Three families with oculocutaneous albinism type 1 and 95 unrelated healthy Chinese individuals with normal pigmentation were screened for mutations in the TYR gene by direct sequencing.
The Q402 allele has been associated with autosomal recessive ocular albinism when it is in trans with a tyrosinase gene mutation associated with oculocutaneous albinism type 1.
Mutations in the TYR gene (TYR, 11q14-21, MIM 606933) cause oculocutaneous albinism type 1 (OCA1, MIM 203100), a developmental disorder having an autosomal recessive mode of inheritance.
Oculocutaneous albinism type 1 (OCA1) results from mutations in the tyrosinase gene, which lead to partial or complete loss of activity of the corresponding enzyme.
Identification of active site residues involved in metal cofactor binding and stereospecific substrate recognition in Mammalian tyrosinase. Implications to the catalytic cycle.