中科院上海生命科学研究院上海交通大学医学院健康科学研究所孔祥银研究员带领的课题组经过4年多的艰苦努力，在人类皮肤基因研究领域获得重要成果，发现KITLG基因突变引起家族性进行性色素过度沉着症。研究结果近日发表在国际主流杂志《美国人类遗传学》。（The American Journal of Human Genetics）
人类通过进化形成不同皮肤颜色。白种人皮肤是白色的，黑种人皮肤是黑色的，而黄种人皮肤则是黄色的。同一人种不同地区、不同个体，甚至同一个体不同身体部位肤色也有差别。 皮肤颜色改变也是常见的临床体征，涉及临床各科疾病。但是，决定皮肤颜色的分子机制并不是非常清楚。
据介绍，家族性进行性色素过度沉着症是一种常染色体显性遗传疾病，患者在出生早期皮肤会出现色素沉着斑，且色素斑的数量和面积会随着年龄的增长而增加，病因并不清楚。
孔祥银课题组对一个中国人（山东）家族性进行性色素过度沉着症家系进行了研究，王志强博士等人发现引起进行性色素沉着的致病基因突变（sKITLGN36S）。进一步的功能研究表明, KITLG突变是一个获得功能性突变，能增加色素细胞黑色素的数量。“这一工作加深了人们对皮肤颜色形成机理的认识，对于色素沉着性疾病的防治、化妆品的研发等都有指导意义。”专家评价。
该工作得到了国家科技部、国家自然科学基金委和中科院项目的支持。（生物谷Bioon.com）
生物谷推荐原始出处：
The American Journal of Human Genetics, 16 April 2009 doi:10.1016/j.ajhg.2009.03.019
Gain-of-Function Mutation of KIT Ligand on Melanin Synthesis Causes Familial Progressive Hyperpigmentation
Zhi-Qiang Wang1,2,5,Lizhen Si1,2,5,Quan Tang1,2,Debao Lin3,6,Zhangjie Fu1,2,Jing Zhang1,2,Bin Cui1,2,Yufei Zhu1,2,Xianghua Kong4,Min Deng1,2,Yu Xia1,2,Heng Xu1,2,Weidong Le1,2,Landian Hu1,2andXiangyin Kong1,2,,
1 State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, P.R. China
2 Institute of Health Science, Shanghai Institutes for Biological Sciences of the Chinese Academy of Sciences, Shanghai 200025, P.R. China
3 Department of Dermatology, Guiyang Medical College, Guiyang, Guizhou 550001, P.R. China
4 Clinical Laboratory, Affiliated Hospital of Binzhou Medical College, Binzhou, Shandong 256603, P.R. China
5 These authors contributed equally to this work
6 Present address: Department of Dermatology, Cangshan Skin Disease Prevention and Control Station, Shandong 277700, P.R. China
Familial progressive hyperpigmentation (FPH) is an autosomal-dominantly inherited disorder characterized by hyperpigmented patches in the skin, present in early infancy and increasing in size and number with age. The genetic basis for FPH remains unknown. In this study, a six-generation Chinese family with FPH was subjected to a genome-wide scan for linkage analysis. Two-point linkage analysis mapped the locus for FPH at chromosome 12q21.31-q23.1, with a maximum two-point LOD score of 4.35 ( = 0.00) at D12S81. Haplotype analysis confined the locus within an interval of 9.09 cM, flanked by the markers D12S1667 and D12S2081. Mutation profiling of positional candidate genes detected a heterozygous transversion (c. 107AG) in exon 2 of the KIT ligand (KITLG) gene, predicted to result in the substitution of a serine residue for an asparagine residue at codon 36 (p.NS). This mutant G allele cosegregated perfectly with affected, but not with unaffected, members of the FPH family. Function analysis of the soluble form of sKITLG revealed that mutant sKITLGN36S increased the content of the melanin by 109% compared with the wild-type sKITLG in human A375 melanoma cells. Consistent with this result, the tyrosinase activity was significantly increased by mutant sKITLGN36S compared to wild-type control. To our knowledge, these data provided the first genetic evidence that the FPH disease is caused by the KITLGN36S mutation, which has a gain-of-function effect on the melanin synthesis and opens a new avenue for exploration of the genetic mechanism of FPH.
