全外显子组测序发现FUT6基因在1例糖尿病肾病中的终止突变  

Exome sequencing identified a FUT6 nonsense mutation in one diabetic nephropathy patient

作　　者：王玉华[1] 蔡春友[1] 李卫东[1] 韩鸿玲[2] 

机构地区：[1]天津医科大学基础医学研究中心,天津300070 [2]天津医科大学总医院肾脏科,天津300052

出　　处：《天津医科大学学报》2015年第1期18-21,共4页Journal of Tianjin Medical University

基　　金：国家自然科学基金资助项目(81070576);天津市自然科学基金重点项目(12JCZDJC24700)

摘　　要：目的:检测与糖尿病肾病相关的致病基因。方法:应用外显子捕获技术和高通量测序技术对1例临床病理确诊的糖尿病肾病患者的全基因组外显子进行测序,将测序数据筛选出的可能对基因功能有影响的非同义突变和剪切位点突变,与公共数据库YH、db SNP129、8Hap Mapexome和db SNP thousands genome进行对比过滤,然后对筛选出的候选基因进行免疫组化染色研究其表达量的变化。结果:通过数据的对比过滤,共发现509个突变位点,其中包括497个错义突变和12个无义突变。发生无义突变并且在肾脏高表达的基因有ANKRD35、ACSM2A、FUT6和HAAO。其中FUT6基因的315TAC>TAA,氨基酸残基由酪氨酸突变为终止密码子,免疫组化证实FUT6在该患者的肾活检组织中表达量减少。结论:糖尿病肾病患者中发现FUT6基因终止突变及其表达的显著降低,提示FUT6可能与糖尿病肾病的发病有关。Objective： To identify plausible disease causing mutations in the diabetic nephropathy （DN）. Methods： Exome capturing and high-throughput sequencing were used to detect mutations of DN related genes in a patient confirmed by pathological diagnosis. Novel non- synonymous and splice acceptor/douor site mutations were identified after screening reported polymorphisms in public databases （YH, dbSNP129, eight HapMap exomes and 1 000 Genome variant database）. [mmunohistoehemistry was performed in renal biopsy specimen to verify expression changes of genes with nonsense mutations. Results： Five hundred and nine novel mutations were identified in the DN patient, including 497 missense mutations and 12 nonsense mutations. In 12 genes with stop codon mutations, ANKRD35, ACSM2A, FUT6, and HAAO were normally highly expressed in kidney. A mutation of codon 315 TAC 〉TAA in the FUT6 gene, changed the amino acid sequencing from Tyr stop codon. Immunohistochemistry confirmed the decreased FUT6 expression in renal biopsies of the DN patient. Conclusion： This research identifies a stop codon mutation of the FUT6 gene in a DN patient, and the expression level of the FUT6 gene decreases significantly in the patient＇s renal biopsy. The FUT6 stop codon mutation may be associated with the etiology of DN in that patient.

关 键 词：糖尿病肾病 全基因组外显子测序 FUT6 

分 类 号：R587.1[医药卫生—内分泌] R394[医药卫生—内科学]