KIT杂合大片段缺失导致斑驳病一家系的临床表型  

Phenotype of piebaldism resulted from heterozygous large fragment KIT deletion in one family

作　　者：张睿 谭妍 马东来 王蓉蓉[1] 张学[1] ZHANG Rui;TAN Yan;MA Donglai;WANG Rongrong;ZHANG Xue(McKusick-Zhang Center for Genetic Medicine,State Key Laboratory for Complex Severe and Rare Diseases,Institute of Basic Medical Sciences CAMS,School of Basic Medicine PUMC,Beijing 100005;Department of Dermatology,National Clinical Research Center for Skin and Immune Diseases,State Key Laboratory of Complex Severe and Rare Diseases,Peking Union Medical College Hospital,CAMS&PUMC,Beijing 100730,China)

机构地区：[1]中国医学科学院基础医学研究所,北京协和医学院基础学院,麦库西克-张孝骞协和遗传医学中心,疑难重症及罕见病国家重点实验室,北京100005 [2]中国医学科学院,北京协和医学院,北京协和医院,皮肤科,疑难重症及罕见病国家重点实验室,国家皮肤与免疫疾病临床医学研究中心,北京100730

出　　处：《基础医学与临床》2024年第7期954-958,共5页Basic and Clinical Medicine

基　　金：国家重点研发计划(2022YFC2703900);国家自然科学基金(82394420、82394423);中国医学科学院医学与健康科技创新工程(2021-I2M-1-018)。

摘　　要：目的鉴定一个斑驳病家系的致病基因突变。方法收集斑驳病患者及其家系成员的临床资料,采集外周血,进行全外显子组测序。通过qPCR验证目的基因的缺失;采用gap-PCR结合Sanger测序法确定具体缺失的大小以及位点。结果在先证者4号染色体上存在约1.74 Mb的杂合大片段缺失突变,其中包括了全部KIT(斑驳病的致病基因)。该缺失在家系中呈基因型-表型共分离,在dbSNV数据库中未见该区域的缺失报道。该缺失是目前报道的最小的因KIT全长缺失而导致斑驳病表型的片段缺失。结论KIT缺失是导致该家系斑驳病表型的原因。Objective To identify the pathogenic mutations in a family with piebaldism.Methods Clinical infor⁃mation and peripheral blood were collected from the patient with piebaldism and their parents.Whole exome se⁃quencing was performed to identify the potential pathogenic mutations.QPCR was used to determine the deletion of the target gene,while gap⁃PCR and Sanger sequencing was used to determine the size and the specific deletion site.Results The proband had a heterozygous deletion mutation of approximately 1.74 Mb located at chromosome 4,in⁃cluding a full length of the pathogenic gene KIT for mottled disease and it was the smallest micro deletion causing isolated piebaldism due to the loss of the KIT.Conclusions The heterozygous deletion including the KIT is a poten⁃tial cause of the piebaldism phenotype found in this family.

关 键 词：斑驳病 基因缺失 KIT 基因诊断 拷贝数变异(CNV) 

分 类 号：R596.2[医药卫生—内科学]