RAPID COMMUNICATION Mutations in the MATP Gene in Five German Patients Affected by Oculocutaneous Albinism Type 4 Uta Rundshagen, 1 Christine Zu ¨hlke, 1n Sven Opitz, 1 Eberhard Schwinger, 1 and Barbara Ka ¨smann-Kellner 2 1 Institut fu¨r Humangenetik derUniversita ¨t Lu ¨beck, Lu ¨beck, Germany; 2 Augenklinik der Universita ¨t des Saarlandes, Homburg (Saar), Germany Communicated by Mark H. Paalman Oculocutaneous albinism (OCA) is caused by a deficiency of melanin synthesis and characterized by generalized hypopigmentation of skin, hair, and eyes. Due to the hypopigmentation of the retinal pigment epithelium, OCA is usually associated with congenital visual impairment, in addition to an increased risk of skin cancer. OCA is a genetically heterogeneous disease with distinct types resulting from mutations in different genes involved in the pathway which results in pigmentation. OCA1 is associated with mutations in the TYR gene encoding tyrosinase. OCA2 results from mutations in the P gene encoding the P protein and is the most common form of OCA. OCA3, also known as rufous/red albinism, is caused by mutations in the TYRP1 gene, which encodes the tyrosinase-related protein 1. Recently, OCA4 was described as a new form of OCA in a single patient with a splice site mutation in the MATP gene (or AIM1), the human ortholog of the murine underwhite gene. The similarity of MATP to transporter proteins suggests its involvement in transport functions, although its actual substrate is still unclear. We screened 176 German patients with albinism for mutations within the MATP gene and identified five individuals with OCA4. In this first report on West European patients, we describe 10 so far unpublished mutations, as well as two intronic variations, in addition to two known polymorphisms. Hum Mutat 23:106–110, 2004. r 2003 Wiley-Liss, Inc. KEY WORDS: albinism; oculocutaneous albinism; OCA; MATP; AIM1; OCA4 DATABASES: MATP – OMIM: 606202, 606574 (OCA4); GenBank: NT _ 006576.13, (genomic contig) AF172849, NM _ 016180.2 (mRNA) INTRODUCTION Albinism represents a group of genetically hetero- geneous hereditary abnormalities of melanin pigment synthesis that result in a deficiency or complete absence of melanin in affected individuals. A reduction of melanin causes hypopigmentation of hair and skin, leading to an increased sensitivity to ultraviolet radiation and a predisposition to skin cancer. In the visual system, the deficiency of melanin during fetal and postpartum development of the retinal and cerebral branches of the visual system results in severe alterations such as foveal dysplasia and abnormal routing of the optic nerves, which subsequently leads to a congenital visual impairment, nystagmus, and often strabismus [Creel et al., 1990]. The lack of melanin may either be restricted to the eye (ocular albinism, OA), or it can involve skin, hair, and eyes (oculocuta- neous albinism, OCA). Several genes have been found to be associated with human pigmentation. Mutations of these genes may cause at least four genetic types of recessively inherited OCA. Mutations in the tyrosinase encoding gene, the rate-limiting enzyme in melanin synthesis [Jimbow et al., 1976], are associated with OCA1 (MIM# 203100) [Kwon et al., 1987; Giebel et al., 1991]. Mutations in the human gene encoding the P protein, which probably functions as a transporter, result in OCA2 (MIM# 203200), the most common form of OCA [Rinchik et al., 1993; Puri et al., 1997]. OCA3, also known as rufous or red albinism, is caused by mutations in the gene encoding the tyrosinase-related protein 1 (TYRP1; MIM# 115501), and is a rare form of OCA [Boissy et al., 1996; Jime ´nez-Cervantes et al., 1994]. In 2001, a mutation analysis of the human membrane- associated transporter protein (MATP) gene (MIM# 606202), also known as the melanoma antigen named ‘‘altered in melanoma’’ (AIM1) [Harada et al., 2001] was published by Newton et al. [2001]. Among more than 100 patients with albinism, a homozygous G4A Received 15 July 2003; accepted revised manuscript 17 October 2003. n Correspondence to: Christine Zˇhlke, Institut fˇr Humangenetik, RatzeburgerAllee160, D ^ 23538 Lˇbeck, Germany. E-mail: zuehlke@uni-luebeck.de DOI 10.1002/humu.10311 Published online inWiley InterScience (www.interscience.wiley.com). r r 2003 WILEY-LISS, INC. HUMAN MUTATION 23:106^110 (2004)