中科院上海生命科學(xué)研究院上海交通大學(xué)醫(yī)學(xué)院健康科學(xué)研究所孔祥銀研究員帶領(lǐng)的課題組經(jīng)過4年多的艱苦努力,，在人類皮膚基因研究領(lǐng)域獲得重要成果,，發(fā)現(xiàn)KITLG基因突變引起家族性進行性色素過度沉著癥。研究結(jié)果近日發(fā)表在國際主流雜志《美國人類遺傳學(xué)》,。（The American Journal of Human Genetics）
人類通過進化形成不同皮膚顏色,。白種人皮膚是白色的，黑種人皮膚是黑色的,，而黃種人皮膚則是黃色的,。同一人種不同地區(qū)、不同個體,，甚至同一個體不同身體部位膚色也有差別,。 皮膚顏色改變也是常見的臨床體征，涉及臨床各科疾病,。但是,，決定皮膚顏色的分子機制并不是非常清楚,。
據(jù)介紹，家族性進行性色素過度沉著癥是一種常染色體顯性遺傳疾病,，患者在出生早期皮膚會出現(xiàn)色素沉著斑,，且色素斑的數(shù)量和面積會隨著年齡的增長而增加，病因并不清楚,。
孔祥銀課題組對一個中國人（山東）家族性進行性色素過度沉著癥家系進行了研究,，王志強博士等人發(fā)現(xiàn)引起進行性色素沉著的致病基因突變（sKITLGN36S）。進一步的功能研究表明, KITLG突變是一個獲得功能性突變,，能增加色素細胞黑色素的數(shù)量,。“這一工作加深了人們對皮膚顏色形成機理的認識，對于色素沉著性疾病的防治,、化妝品的研發(fā)等都有指導(dǎo)意義,。”專家評價。
該工作得到了國家科技部,、國家自然科學(xué)基金委和中科院項目的支持,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
