Tyrosinase gene mutations in oculocutaneous albinism�1 (OCA1): definition of the phenotype

Abstract

Oculocutaneous albinism (OCA) is a common human genetic condition resulting from mutations in at least twelve different genes. OCA1 results from mutations of the tyrosinase gene and presents with the life-long absence of melanin pigment after birth (OCA1A) or with the development of minimal-to-moderate amounts of cutaneous and ocular pigment (OCA1B). Other types of OCA have variable amounts of cutaneous and ocular pigment. We hypothesized that white hair at birth indicates OCA1 and tested this in a sample of 120 probands with OCA and white hair at birth. We found that 102 (85%) of the probands had OCA1 with one or two identifiable tyrosinase gene mutations, with 169 (83%) of the 204 OCA1 tyrosinase gene alleles having identifiable mutations and 35 (17%) having no identifiable change in the coding, splice junction, or proximal promoter regions of the gene. The inability to identify the mutation was more common with OCA1B (24/35, 69%) than with OCA1A (11/35, 31%) alleles. Seven probands with no tyrosinase gene mutations were found to have OCA2 with one or two P gene mutations, and in eleven, no mutations were detected in either gene. We conclude that (1) the presence of white hair at birth is a useful clinical tool suggesting OCA1 in a child or adult with OCA, although OCA2 may also have this presentation; (2) the molecular analysis of the tyrosinase and P genes are necessary for precise diagnosis; and (3) the presence of alleles without identifiable mutations of the tyrosinase gene, particularly in OCA1B, suggests that more complex mutation mechanisms of this gene are common in OCA.

Transcriptome expression profiling of fur color formation in domestic rabbits using Solexa sequencing

“…TYR, TYRP1, and TYRP2 constitute the tyrosinase gene family and their products catalyze specific reactions during melanin synthesis (Jimbow, 1999). Tyrosinase is encoded by tyrosinase genes at the albino locus, and functional mutation of tyrosinase genes leads to albinism, which has been demonstrated in mice, rabbits, humans, and cows (Aigner et al, 2000;King et al, 2003;Scullin et al, 2003;Schmutz et al, 2004).…”

Inheritance of a novel mutated allele of the OCA2 gene associated with high incidence of oculocutaneous albinism in a Polynesian community

“…25 Type I OCA has been extensively studied and divided into two clinical subtypes; OCA1A is caused by the complete loss of catalytic activity of the tyrosinase enzyme (TYR) and results in the life-long absence of melanin pigment, whereas OCA1B retains residual tyrosinase function allowing for the development of some melanin pigment. 20,26 The two other forms of albinism, OCA3 and OCA4, have been found to result from mutations in the TYRP1 and SLC45A2 gene loci, respectively. The TYRP1 locus has been mapped to chromosome 9p23, and 95% of OCA3-related mutations result in the generation of premature stop codons or frameshifts producing truncated proteins.…”

Detection of 53 novel DNA variations within the tyrosinase gene and accumulation of mutations in 17 patients with albinism

“…Electronic mutation databases (Albinism Database and Human Gene Mutation Database, www.hgmd.org/ and www.cbc.umn.edu/tad/) list over 100 mutations and polymorphisms in the tyrosinase gene. The majority of mutations have been detected by the groups of Oetting & King (1992, 1993Oetting et al, 1998;King et al, 2003) and Spritz (Fukai et al, 1995;Spritz et al, 1997;Park et al, 1997).…”