Most types of human oculocutaneous albinism (OCA) result from mutations in the 
gene for tyrosinase (OCA1) or the P protein (OCA2), although other types of OCA 
have been described but have not been mapped to specific loci. Melanocytes were 
cultured from an African-American with OCA, who exhibited the phenotype of Brown 
OCA, and his normal fraternal twin. Melanocytes cultured from the patient with 
OCA and the normal twin appeared brown versus black, respectively. Melanocytes 
from both the patient with OCA and the normal twin demonstrated equal amounts of 
NP-40-soluble melanin; however, melanocytes from the patient with OCA contained 
only 7% of the amount of insoluble melanin found from the normal twin. 
Tyrosinase- related protein-1 (TRP-1) was not detected in the OCA melanocytes by 
use of various anti-TRP-1 probes. Furthermore, transcripts for TRP-1 were absent 
in cultured OCA melanocytes. The affected twin was homozygous for a single-bp 
deletion in exon 6, removing an A in codon 368 and leading to a premature stop 
at codon 384. Tyrosine hydroxylase activity of the OCA melanocytes was 
comparable to controls when assayed in cell lysates but was only 30% of controls 
when assayed in intact cells. We conclude that this mutation of the human TRP-1 
gene affects its interaction with tyrosinase, resulting in dysregulation of 
tyrosinase activity, promotes the synthesis of brown versus black melanin, and 
is responsible for a third genetic type of OCA in humans, which we classify as 
"OCA3."