摘要
目的对一个线粒体DNA耗竭综合征家系进行遗传基因变异分析,探讨其分子发病机制。方法提取家系中患者及其父母外周血基因组DNA,采用高通量测序技术检测致病基因变异,并对变异进行Sanger测序验证。结果发现患者DGUOK基因存在c.505_508delTATC的纯合变异,父母都是该位点的杂合变异携带者。c.505_508delTATC为未见报道的新变异位点,造成169位氨基酸由酪氨酸(Y)变异为精氨酸(R),随后编码框改变,在199位翻译提前终止,理论上产生截短蛋白p.Y169Rfs31X。结论c.505_508delTATC为DGUOK基因致病性变异,扩展了DGUOK基因变异谱。
Objective To explore the molecular etiology for a Chinese family with mitochondrial DNA depletion syndrome.Methods Genomic DNA was extracted from peripheral blood samples of the patient and her parents.Targeted capture and next-generation sequencing was carried out to detect potential variants.Suspected variant was validated by Sanger sequencing.Result A novel homozygous frameshift variant c.505_508delTATC was identified in the patient,for which both his mother and father were carriers.Conclusion The frameshift variant c.505_508delTATC probably underlies the mitochondrial DNA depletion syndrome in this patient.The result also enriched the variant spectrum of DGUOK gene.
作者
贾程芳
彭薇
杨晓
杨尧
Jia Chengfang;Peng Wei;Yang Xiao;Yang Yao(Department of Endocrinology and Metabolism,Sir Run Run Shaw Hospital School of Medicine,Zhejiang University,Hangzhou,Zhejiang 310016,China;Bayi Children’s Hospital,the Seventh Medical Center of PLA General Hospital,National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology,Beijing Key Laboratory of Pediatric Organ Failure,Beijing 100700,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2020年第4期410-414,共5页
Chinese Journal of Medical Genetics
基金
国家重点研发计划(2016YFC1000707)。