摘要
目的探讨1个线粒体DNA耗竭综合征8A型家系的临床特点和致病基因。方法对患儿进行全外显子测序筛查潜在的基因变异,Sanger测序进行家系验证,并用PolyPhen-2与PROVEAN软件预测氨基酸变异对蛋白功能的影响。结果患儿,女,2个月4天,临床表现为喂养困难、呼吸急促、肌张力低下等,实验室辅助检查提示患儿发育落后,肝脏、肾脏和心脏功能均异常,并伴有高乳酸血症,因治疗效果差于3月龄时死亡。测序结果显示患儿的RRM2B基因存在c.16delA(p.R6Gfs*22)和c.175G>C(p.A59P)复合杂合变异,分别遗传自其父亲和母亲,均为新鉴定的致病性变异。结论RRM2B基因的c.16delA(p.R6Gfs*22)和c.175G>C(p.A59P)的复合杂合变异可能是线粒体DNA缺失综合征8A型的致病基因,本研究结果加强了对该类疾病的临床特征和遗传学病因认识,同时扩展了RRM2B基因变异谱。
Objective To analyze the clinical characteristics and pathogenic gene in a Chinese pedigree affected with mitochondrial DNA depletion syndrome 8A(MTDPS8A).Methods Whole-exome sequencing was carried out for the patient.Sanger sequencing was used to verify the results,and PolyPhen-2 and PROVEAN software were used to predict the impact of amino acid changes on the function of the protein.Results The patient,a two-month-old female,was admitted to the hospital for poor milk intake and poor mental response.Her clinical manifestations included feeding difficulty,shortness of breath and low muscle tone.Auxiliary laboratory test indicated that the infant was underdeveloped with abnormal liver,kidney,and heart functions accompanied by hyperlacticacidemia.She responded poorly to treatment and eventually died.Sequencing revealed that the child has carried compound heterozygous missense variants of the RRM2B gene,namely c.16delA(p.R6Gfs*22)and c.175G>C(p.A59P),which were respectively inherited from her father and mother,and both were newly discovered pathologic variants.Conclusion The c.16delA and c.175G>C compound heterozygous variants of the RRM2B gene probably underlay the pathogenesis of MTDPS8A.Above finding has strengthened the understanding of the clinical feature and genetic etiology of this disease and expanded the mutation spectrum of the RRM2B gene.
作者
王彦红
郑璇
王向蝶
张小慢
郭鹏波
刘磊
梅世月
Wang Yanhong;Zheng Xuan;Wang Xiangdie;Zhang Xiaoman;Guo Pengbo;Liu Lei;Mei Siyue(Henan Provincial Neurodevelopment Engineering Research Center for Children,Henan Provincial Key Laboratory for Children’s Genetic and Metabolic Diseases,Children’s Hospital Affiliated to Zhengzhou University,Henan Provincial Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou,Henan 450018,China;Pediatric Intensive Care Unit,Children’s Hospital Affiliated to Zhengzhou University,Henan Provincial Children’s Hospital,Zhengzhou Children’s Hospital,Zhengzhou,Henan 450018,China)
出处
《中华医学遗传学杂志》
CAS
CSCD
2022年第1期26-30,共5页
Chinese Journal of Medical Genetics
基金
国家自然科学基金(81701125)
河南省科技攻关项目(182102310418)。
