Tyrosinase gene (TYR) mutations in Chinese patients with oculocutaneous albinism type 1

Abstract

We have identified five different TYR mutations, including one novel mutation, which caused oculocutaneous albinism type 1 in Chinese. Further analysis of the patients will be useful to determine the effects of these mutations on the tyrosinase activities.

Two Novel Tyrosinase (TYR) Gene Mutations with Pathogenic Impact on Oculocutaneous Albinism Type 1 (OCA1)

“…Furthermore, cysteine residues in tyrosinase play an important role in the proper folding and maintenance of the tyrosinase tertiary structure in humans [31]. Alterations of these cysteine residues, such as C89S mutations in exon 1 could inactivate the protein and cause OCA1 [3]. Therefore, C89S could be considered as a pathogenic mutation.…”

“…Other subtypes of OCA include OCA type 2 (OCA2, MIM#203200) caused by mutations in the OCA2 gene (15q11.2–q12), OCA type 3 (OCA3, MIM#203290) associated with mutations in the tyrosinase-related protein gene (TYRP1, 9p23) and OCA type 4 (OCA4, MIM#606574) because of mutations in the membrane-associated transporter gene (MATP, 5p13.3) [3]. The prevalence of different forms of OCA fluctuates widely in different populations [4], where OCA1 is the most common subtype found in Caucasians and accounts for about 50% of all cases worldwide [5], [6], while OCA2 is most common in Africa and accounts for about 30% of all cases worldwide [7].…”

Melanogenesis and antioxidant defense system in normal human melanocytes cultured in the presence of chlorpromazine

“…Melanins are secreted from melanocytes to neighboring keratinocytes, where they provide skin pigmentation and protect against ultraviolet radiation (Plonka et al, 2009;Rok et al, 2012). Tyrosinase is the key enzyme in melanogenesis, which catalyzes the hydroxylation of tyrosine to dihydroxyphenylalanine (DOPA) as well as the subsequent oxidation of DOPA to DOPAquinone -common step for biosynthesis of both types of melanin: eumelanin and pheomelanin (Liu et al, 2010;Otrę ba et al, 2012;Schallreuter et al, 2008). DOPAquinone is converted to DOPAchrome, which undergoes a spontaneous decarboxylation to 5,6-dihydroxyindole (DHI) or an enzymatic tautomerization (by tyrosinase-related protein TRP2) to 5,6-dihydroxyindole-2-carboxylic acid (DHICA).…”

Identification of a missense mutation in the tyrosinase gene in a Chinese family with oculocutaneous albinism type 1

“…Mutations in the TYR gene lead to decreased or even absent tyrosinase enzyme activity, and subsequently, a decreased or complete loss of melanin synthesis. Numerous missense mutations are located in or adjacent to the copper binding sites, and interrupt the normal function of tyrosinase, by affecting copper binding or by disrupting the substrate binding site (17).…”