一个肢带型肌营养不良症1F家系的TNPO3基因变异及临床表型分析  

Analysis of TNPO3 gene variant and clinical phenotype in a neonate with limb-girdle muscular dystrophies form 1F

作　　者：高敏[1] 侯良超 张开慧[1] 律玉强 马健[1] 王东[1] 盖中涛[1] 刘毅[1] Gao Min;Hou Liangchao;Zhang Kaihui;Lyu Yuqiang;Ma Jian;Wang Dong;Gai Zhongtao;Liu Yi(Pediatric Research Institute,Children′s Hospital Affiliated Shandong University(Jinan Children′s Hospital),Jinan,Shandong 250022,China;Department of Neonatal Surgery,Children′s Hospital Affiliated Shandong University(Jinan Children′s Hospital),Jinan,Shandong 250022,China)

机构地区：[1]山东大学附属儿童医院(济南市儿童医院)儿科研究所,济南250022 [2]山东大学附属儿童医院新生儿外科,济南250022

出　　处：《中华医学遗传学杂志》2022年第9期979-982,共4页Chinese Journal of Medical Genetics

基　　金：济南市卫生健康委员会科技计划项目 (2019-2-32)。

摘　　要：目的明确1例发育迟缓患儿的遗传学病因。方法对患儿进行临床和实验室检查,并抽取患儿及其父母的外周静脉血样,应用二代目标区域捕获测序技术对患儿进行遗传病疾病相关基因的检测,对可疑变异位点进行保守性及致病性预测,并进行患儿及其父母的Sanger测序验证。结果男,4个月11天,临床表现发育迟缓,四肢肌力低,基因检测示患儿TNPO3基因存在c.1432C>T,为新发现的变异,母亲为携带者。该变异为无义变异,造成蛋白翻译的提前终止,生物学软件预测其具有致病性。结论TNPO3基因的c.1432C>T变异引起肢带型肌营养不良症1F,可能是患儿的遗传学病因。这是国内首例病例报道,该病例的发现丰富了TNPO3基因的变异数据库。Objective To explore the genetic basis for a neonate featuring developmental delay.Methods Clinical examination and laboratory tests were carried out for the patient.Peripheral venous blood samples of the proband and his parents were extracted and subjected to target capture next generation sequencing.Candidate variant was verified by Sanger sequencing.Results The patient,a four-month-old male,has presented with developmental delay and weakness of limbs.Genetic testing revealed that he had harbored a novel c.1432C>T variant of the TNPO3 gene,which was inherited from his mother.The nonsense variant has resulted in premature termination of protein translation and was predicted to be pathogenic by bioinformatic analysis.Conclusion The heterozygous c.1432C>T variant of the TNPO3 gene probably underlay the limb-girdle muscular dystrophies form 1F in this patient.Above finding has enriched the mutational spectrum of the TNPO3 gene.

关 键 词：肢带型肌营养不良症1F 肌无力 KDM5C基因 新变异 

分 类 号：R746.2[医药卫生—神经病学与精神病学]