title: Mutations in ABCB6 cause dyschromatosis universalis hereditaria.
abstract: Dyschromatosis universalis hereditaria (DUH) is a pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed randomly over the body. No causative genes have been reported to date. In this study, we investigated a large five-generation Chinese family with DUH. After excluding the two known DUH loci, we performed genome-wide linkage analysis and identified a DUH locus on chromosome 2q33.3-q36.1 with a maximum LOD score of 3.49 with marker D2S2382. Exome sequencing identified a c.1067T>C (p.Leu356Pro) mutation in exon 3 of ABCB6 (ATP-binding cassette subfamily B, member 6) in the DUH family. Two additional missense mutations, c.508A>G (p.Ser170Gly) in exon 1 and c.1736G>A (p.Gly579Glu) in exon 12 of ABCB6, were found in two out of six patients by mutational screening using sporadic DUH patients. Immunohistologic examination in biopsy specimens showed that ABCB6 is expressed in the epidermis and had a diffuse cytoplasmic distribution. Examination of subcellular localization of wild-type ABCB6 in a B16 mouse melanoma cell line revealed that it is localized to the endosome-like compartment and dendrite tips, whereas disease-causing mutations of ABCB6 resulted in its retention in the Golgi apparatus. Our studies identified ABCB6 as the first pathogenic gene associated with DUH. These findings suggest that ABCB6 may be a physiological factor for skin pigmentation.
authors.affiliation: Department of Anesthesiology, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Caie
authors.initials: C
authors.lastname: Zhang
authors.forename: Duanzhuo
authors.initials: D
authors.lastname: Li
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhang
authors.forename: Xingping
authors.initials: X
authors.lastname: Chen
authors.forename: Mi
authors.initials: M
authors.lastname: Huang
authors.forename: Stephen
authors.initials: S
authors.lastname: Archacki
authors.forename: Yuke
authors.initials: Y
authors.lastname: Tian
authors.forename: Weiping
authors.initials: W
authors.lastname: Ren
authors.forename: Aihua
authors.initials: A
authors.lastname: Mei
authors.forename: Qingyan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Mingyan
authors.initials: M
authors.lastname: Fang
authors.forename: Zheng
authors.initials: Z
authors.lastname: Su
authors.forename: Ye
authors.initials: Y
authors.lastname: Yin
authors.forename: Dongxian
authors.initials: D
authors.lastname: Liu
authors.forename: Yingling
authors.initials: Y
authors.lastname: Chen
authors.forename: Xiukun
authors.initials: X
authors.lastname: Cui
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Mugen
authors.initials: M
authors.lastname: Liu
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Deng
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002648:Child; D002889:Chromosomes, Human, Pair 2; D005260:Female; D005799:Genes, Dominant; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D010859:Pigmentation Disorders / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000473:pathology; D012873:Skin Diseases, Genetic / Q000235:genetics* / Q000473:pathology; D012880:Skin Pigmentation / Q000235:genetics*
chemical_list: C107991:ABCB6 protein, human; D018528:ATP-Binding Cassette Transporters