title: Molecular bases of congenital hypopigmentary disorders in humans and oculocutaneous albinism 1 in Japan.
abstract: The molecular bases of various types of congenital hypopigmentary disorders have been clarified in the past 10 years. Homozygous gene mutations of enzymes functional in melanogenesis such as tyrosinase, P protein and DHICA oxidase, result in oculocutaneous albinism (OCA) 1, OCA 2, and OCA 3, respectively. The genes responsible for Hermansky-Pudlak syndrome (HPS) and Chediak-Higashi syndrome (CHS) have also recently been isolated and cloned. The transcription factor paired box 3 (PAX3) works at the promoter region of the microphthalmia-associated transcription factor (MITF) gene, and the MITF transcription factor orders the expression of c-kit, which encodes the receptor for stem-cell factor, which in turn stimulates melanoblast migration from the neural tube to the skin in the embryo. Heterozygous mutations of PAX3, MITF, or c-kit genes induce Waardenburg syndrome (WS) 1/3, WS 2 or Piebaldism, respectively. A defect of endothelin-3 or the endothelin-B receptor produces WS 4. In our examination of 26 OCA 1 patients in Japan, all were found to have homozygous or heterozygous tyrosinase gene mutations at codons 77 or 310. Therefore, mutations at codons 77 and 310 are the major ones in Japanese patients with OCA 1. An autosomal dominant pigmentary disease of dyschromatosis symmetrica hereditaria (DSH) is well known in Japan, and is characterized by a mixture of hypo- and hyper-pigmented macules of various sizes on the backs of the hands and feet. The disease gene and its chromosomal localization have not been identified yet. Our trial of linkage analysis and positional cloning to determine the disease gene is presented.
authors.affiliation: Department of Dermatology, Nagoya University School of Medicine, Japan. tomita@med.nagoya-u.ac.jp
authors.forename: Y
authors.initials: Y
authors.lastname: Tomita
authors.forename: Y
authors.initials: Y
authors.lastname: Miyamura
authors.forename: M
authors.initials: M
authors.lastname: Kono
authors.forename: R
authors.initials: R
authors.lastname: Nakamura
authors.forename: J
authors.initials: J
authors.lastname: Matsunaga
mesh_terms: D016115:Albinism, Oculocutaneous / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D022861:Hermanski-Pudlak Syndrome / Q000235:genetics; D006801:Humans; D017496:Hypopigmentation / Q000235:genetics*; D007564:Japan; D008565:Membrane Proteins / Q000235:genetics; D026901:Membrane Transport Proteins; D014442:Monophenol Monooxygenase / Q000235:genetics; D016116:Piebaldism / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D014849:Waardenburg Syndrome / Q000235:genetics
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C489600:OCA2 protein, human; D014442:Monophenol Monooxygenase; D019009:Proto-Oncogene Proteins c-kit