先天性角化不良患儿基因分析及端粒长度测定  

Genotype Analysis and Telomere Length Measure in Patients with Dyskeratosis Congenita

作　　者：张家源 安文彬 张丽 常丽贤 戚本泉 刘天峰 刘芳[1] 杨文钰 郭晔 竺晓凡 

机构地区：[1]中国医学科学院、北京协和医学院血液学研究所、血液病医院儿童血液诊疗中心,天津300020

出　　处：《中国实验血液学杂志》2015年第1期212-216,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(81200396,81170470);国家重大科学研究计划(2012CB966603)

摘　　要：目的:对2例先天性角化不良(DC)患儿进行基因分析和端粒长度测定。方法:2例患儿表现为皮肤黏膜异常三联征(指/趾甲角化不良、口腔黏膜白斑、皮肤网状色素沉着)和骨髓衰竭,提取他们的外周血DNA,应用PCR扩增DC的6个热点基因,包括DKC1、TERT、TERC、TINF2、NOP10、NHP2,进行DNA测序和基因分析,并应用流式-原位杂交(Flow-FISH)方法检测患者外周血淋巴细胞相对端粒长度。结果:1例患儿测序发现为TINF2基因中第6号外显子的c.811C>T(Q271X)突变,另1例患儿测序发现为TINF2基因中第6号外显子c.848C>A(P283H)突变,患者相对端粒长度显著低于同年龄正常儿童。结论:低龄患儿出现典型皮肤黏膜改变、骨髓衰竭时,应考虑到DC可能。基因检测及端粒长度测定可避免误诊、漏诊及明确诊断。其中1例患儿TINF2基因中第6号外显子c.811C>T(Q271X)突变,另外1例患儿TINF2基因中第6号外显子c.848C>A(P283H)突变,此发现均为国内首次报道。Objective： To analysze genotype and measure telomere length in two Chinese patients with dyskeratosis congenita（DC）. Methods： The peripleral blood DNA was extracted in two patients characterized by mucocutaneous abnormalities （abnormal nails, lacy reticulated skin pigmentation, and oral leukoplakia）, bone marrow failure, DC genes were amplified by polymerase chain reaction （PCR）, including DKC1,TERT,TERC, TINF2 ,NOP10 ,NHP2, then DNA sequencing was performed for abnormal exons. Lymphocyte telomere length was measured by flow cytometryfluorescence in situ hybridization（Flow-FISH）. Results： Abnormal peaks were found in exon 6 of TINF2 gene of the two patients and a 811C→T transition in TINF2 gene in one patient. DNA sequencing showed a 848C→A transition in TINF2 gene in another patient. Relative telomere length was remarkable less than that of normal children with same age. Condusions： Physician should think about DC if the young patients with mucocutaneous abnormalities and marrow failure. Early detection of related genes and measurernant of tolomere length may contribute to avoid misdiagnosis. TINF2 c. 811C→T（ Q271X ） and TINF2 c. 848C→A（ P283H ） exist in the two patients, it is reported in China for the first time.

关 键 词：先天性角化不良 DNA突变分析 端粒长度测定 

分 类 号：R551.3[医药卫生—血液循环系统疾病]