TY - JOUR
T1 - Mutations in ABCB6 cause dyschromatosis universalis hereditaria
AU - Zhang, Caie
AU - Li, Duanzhuo
AU - Zhang, Jianguo
AU - Chen, Xingping
AU - Huang, Mi
AU - Archacki, Stephen
AU - Tian, Yuke
AU - Ren, Weiping
AU - Mei, Aihua
AU - Zhang, Qingyan
AU - Fang, Mingyan
AU - Su, Zheng
AU - Yin, Ye
AU - Liu, Dongxian
AU - Chen, Yingling
AU - Cui, Xiukun
AU - Li, Chang
AU - Yang, Huanming
AU - Wang, Qing
AU - Wang, Jun
AU - Liu, Mugen
AU - Deng, Yunhua
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/84884413074
U2 - 10.1038/jid.2013.145
DO - 10.1038/jid.2013.145
M3 - 文章
AN - SCOPUS:84884413074
SN - 0022-202X
VL - 133
SP - 2221
EP - 2228
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 9
ER -