title: The mouse pink-eyed dilution gene: association with hypopigmentation in Prader-Willi and Angelman syndromes and with human OCA2.
abstract: Mutations at the mouse pink-eyed dilution locus, p, cause hypopigmentation. We have cloned the mouse p gene cDNA and the cDNA of its human counterpart, P. The region of mouse chromosome 7 containing the p locus is syntenic with human chromosome 15q11-q13, a region associated with Prader-Willi syndrome (PWS) and Angelman syndrome (AS), both of which involve profound imprinting effects. PWS patients lack sequences of paternal origin from 15q, whereas AS patients lack a maternal copy of an essential region from 15q. However, the critical regions for these syndromes are much smaller than the chromosomal region commonly deleted that often includes the P gene. Hypopigmentation in PWS and AS patients is correlated with deletions of one copy of the human P gene that is highly homologous with its mouse counterpart. A subset of PWS and AS patients also have OCA2. These patients lack one copy of the P gene in the context of a PWS or AS deletion, with a mutation in the remaining chromosomal homologue of the P gene. Mutations in both homologues of the P gene of OCA2 patients who do not have PWS or AS have also been detected.
authors.affiliation: Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111.
authors.forename: M H
authors.initials: MH
authors.lastname: Brilliant
authors.forename: R
authors.initials: R
authors.lastname: King
authors.forename: U
authors.initials: U
authors.lastname: Francke
authors.forename: S
authors.initials: S
authors.lastname: Schuffenhauer
authors.forename: T
authors.initials: T
authors.lastname: Meitinger
authors.forename: J M
authors.initials: JM
authors.lastname: Gardner
authors.forename: D
authors.initials: D
authors.lastname: Durham-Pierre
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsu
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D017204:Angelman Syndrome / Q000235:genetics*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005127:Eye Color / Q000235:genetics*; D005260:Female; D005796:Genes; D018392:Genomic Imprinting; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics*; D008297:Male; D008322:Mammals / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D008817:Mice, Mutant Strains; D008958:Models, Molecular; D010375:Pedigree; D011218:Prader-Willi Syndrome / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; C076239:P protein, mouse