title: P gene mutations associated with oculocutaneous albinism type II (OCA2).
abstract: Oculocutaneous albinism type II (OCA2) is the most common form of albinism in humans. OCA2 has been previously associated with mutations of the P gene, the human homologue to the murine pink-eyed dilution gene. The P gene encodes a 110 kDa protein containing 12 potential membrane spanning domains and is associated with melanosomal membranes. The specific function of the P protein is currently unknown but is thought to be involved in tyrosinase processing and transport. We report nine novel mutations in the P gene associated with OCA2. These include two missense mutations, c.1938A>C (p.Ile646Val) and c.1556T>C (p.Val519Ala); one nonsense mutation c.612G>A (p.Trp204X); five frameshift mutations: c.2372_2373delTC, c.1555delG, c.1938_1939insC, c.2050delT, and c.1045_1046delAT; and a splice site mutation c.1951+1G>A. We also report 12 novel polymorphisms including one amino acid substitution, c.2365_2366GC>CA (p.Ala789Glu). At present, there is no functional assay to determine if a mutation is truly pathogenic. The presence of numerous polymorphisms of the P gene in the coding region, several of which result in amino acid substitutions, makes molecular diagnosis problematic. To ensure accurate molecular diagnosis, further mutational analysis will be necessary to produce a comprehensive list of mutations associated with OCA2. This information will also help define the critical functional domains of the P protein. Mutations associated with OCA2 can be found in the Albinism Database (http://albinismdb.med.umn.edu).
authors.affiliation: Department of Medicine, Institute of Human Genetics, University of Minnesota, Minneapolis, Minnesota 55455, USA. bill@lenti.med.umn.edu <bill@lenti.med.umn.edu>
authors.forename: William S
authors.initials: WS
authors.lastname: Oetting
authors.forename: Sarah Savage
authors.initials: SS
authors.lastname: Garrett
authors.forename: Marcia
authors.initials: M
authors.lastname: Brott
authors.forename: Richard A
authors.initials: RA
authors.lastname: King
mesh_terms: D016115:Albinism, Oculocutaneous / Q000145:classification / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005060:Europe / Q000208:ethnology; D005091:Exons / Q000235:genetics; D005127:Eye Color / Q000235:genetics; D005260:Female; D016368:Frameshift Mutation; D005838:Genotype; D006200:Hair Color / Q000235:genetics; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007223:Infant; D007585:Jews / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D020125:Mutation, Missense; D010679:Philippines / Q000208:ethnology; D017354:Point Mutation; D011110:Polymorphism, Genetic; D022821:RNA Splice Sites / Q000235:genetics*; D017384:Sequence Deletion; D044465:White People / Q000235:genetics
chemical_list: D018389:Codon, Nonsense; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D022821:RNA Splice Sites