Mutations in the Human Orthologue of the Mouse underwhite Gene (uw) Underlie a New Form of Oculocutaneous Albinism, OCA4

Abstract

Oculocutaneous albinism (OCA) affects approximately 1/20,000 people worldwide. All forms of OCA exhibit generalized hypopigmentation. Reduced pigmentation during eye development results in misrouting of the optic nerves, nystagmus, alternating strabismus, and reduced visual acuity. Loss of pigmentation in the skin leads to an increased risk for skin cancer. Two common forms and one infrequent form of OCA have been described. OCA1 (MIM 203100) is associated with mutations of the TYR gene encoding tyrosinase (the rate-limiting enzyme in the production of melanin pigment) and accounts for approximately 40% of OCA worldwide. OCA2 (MIM 203200), the most common form of OCA, is associated with mutations of the P gene and accounts for approximately 50% of OCA worldwide. OCA3 (MIM 203290), a rare form of OCA and also known as "rufous/red albinism," is associated with mutations in TYRP1 (encoding tyrosinase-related protein 1). Analysis of the TYR and P genes in patients with OCA suggests that other genes may be associated with OCA. We have identified the mouse underwhite gene (uw) and its human orthologue, which underlies a new form of human OCA, termed "OCA4." The encoded protein, MATP (for "membrane-associated transporter protein") is predicted to span the membrane 12 times and likely functions as a transporter.

Distinctive distribution of AIM1 polymorphism among major human populations with different skin color

“…Human AIM-1 was first identified as a melanoma antigen with unknown function (Harada et al 2001). However, recently, Newton et al (2001) assigned it to the underwhite locus (uw), which tion of non-Caucasians to the present white South African population (Caucasians) is estimated to be about 7% from studies of the HLA human major histocompatibility complex (Botha et al 1975), and this value well accounts for the breakdown of the monomorphic status of Phe (0.89) among the white South Africans in the present study. Newton et al (2001) also reported that L374F is a common polymorphism.…”

“…However, not a little genetic evidence suggests an intervention of AIM-1 in mammalian pigmentation. The cytogenetic location of human AIM1 (5p13.3, NCBI LocusLink; 51151) does not preclude AIM1 from being a candidate for an important pigmentation locus, uw (Sweet et al 1998), and it was, in fact, proved that the AIM1 is responsible for one type of human albinism (Newton et al 2001). In mice, a double mutation of uw and Mc1r results in significantly less pigmentation than either mutation alone (Lehman et al 2000).…”

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

“…29 OCA4 was first defined on presentation in one individual homozygous for a splice-site mutation within the SLC45A2 gene on chromosome 5p, with the phenotype consisting of generalized and ocular hypopigmentation similar to that seen in OCA2 patients. 30 OCA4 is one of the most common forms of albinism in the Japanese population. 31,32 Polymorphism within the SLC45A2 gene is a major determinant of normal variation in skin pigmentation, 33 with the rs16891982 b.1122G/C, p.374Leu/Phe change of the encoded protein, MATP, associated with the lighter pigmentation phenotypes of Europeans.…”

Mutations in SLC45A2 Cause Plumage Color Variation in Chicken and Japanese Quail

“…SLC45A2 mutations have been found in medaka (Fukamachi et al 2001), humans (Newton et al 2001), mouse (Newton et al 2001;Du and Fisher 2002), and horse (Mariat et al 2003). Oculocutaneous albinism type IV (OCA4) in humans is caused by mutations in SLC45A2 (Newton et al 2001).…”