一例重型斑驳病患者的KIT基因突变检测  

Detection of KIT gene of a case with serious phenotypes of piebaldism

作　　者：邓伟平[1] 彭琛 陈敏华[1] 戴少霞[1] 

机构地区：[1]广东省医学科学院//广东省人民医院皮肤科,广东广州510080 [2]上海市皮肤病医院,上海200050

出　　处：《中山大学学报（医学科学版）》2017年第6期949-954,共6页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：广东省自然科学基金(S2013010015872)

摘　　要：【目的】对1例斑驳病小家系中的先证者进行致病基因KIT和SLUG(SNAI2)编码序列的突变检测,寻找致病性突变。【方法】应用PCR扩增KIT和SLUG基因编码区及外显子-内含子交界区,对PCR产物进行直接测序。在50例正常对照中进行新突变的测序分析,以排除多态性。【结果】家系先证者SLUG基因检测未发现异常,KIT基因检测到1个国际数据库中尚未报道的点突变c.860T>A(p.V287E),患者父母均未检测到此突变。该突变位于KIT基因编码蛋白的细胞外配体结合区域,第287位的缬氨酸突变为谷氨酸,可能导致了与249位谷氨酸相排斥,破坏了D3结构域中βD和βD/βE稳定性,最终影响SCF(stem cell factor)的结合功能。【结论】KIT基因的新生突变可能是引起本重型斑驳病患者发病的原因。【Objective】To investigate the mutations of KIT gene and SLUG(SNAI2)gene in one patients with piebaldism in China.【Methods】All coding exons and exon-intron boundaries of KIT gene and SLUG gene were amplified by PCR. The PCR products were sequenced. The DNA samples from 50 normal subjects were also sequenced for control.【Results】The novel mutation,c.860 T>A(p.V287 E),was detected in patient. This mutation was absent in his parents and the controls,indicating a de novo mutation. The detection result of all coding exons and exon-intron boundaries of SLUG gene was normal.This p.V287 E mutation was located in the extracellular ligand-bindingdomain(ectodomain)of KIT,which may generate clash with E249 and disrupt the conformation of βD andβD/βE of D3 that required for SCF(stem cell factor)binding.【Conclusion】We have identified a novel mutation of KIT gene,c.860 T>A(p.V287 E),which is probably associated with serious phenotypes of piebaldism.

关 键 词：斑驳病 KIT基因 SLUG基因 denovo突变 

分 类 号：R758.5[医药卫生—皮肤病学与性病学]