目的 探讨1例HNRNPU基因变异导致神经发育障碍(NDDs)患儿的临床表现及基因变异特征，并检索文献进行回顾性分析。 方法 回顾性分析2020年12月至武汉科技大学附属孝感医院就诊的1例因"间断抽搐1年余"NDDs患儿的临床资料，收集患儿及其父母的外周血样，进行全外显子组测序并进行Sanger测序验证。以"HNRNPU基因""癫痫""癫痫性脑病""遗传性癫痫""神经发育障碍""神经发育综合征"与"epilepsy""epileptic encephalopathy""hereditary epilepsy""neurodevelopmental disorders""neurodevelopmental syndrome""HNRNPU""NDDs"为中英文关键词，检索时间设定为1994年1月1日至2022年2月10日，检索中国知网、万方数据库及PubMed数据库中相关文献并作总结复习。 结果 患儿为2岁男性，5月龄起病，临床表型主要为外貌异常、反复癫痫发作、Gesell量表评估各能区发育商偏低。给予患儿丙戊酸钠抗癫痫发作治疗及康复训练，随访半年内无癫痫发作，但智能及运动发育无明显改善。基因检测患儿HNRNPU基因存在c.1720_1722delCTT(p.Lys574del)杂合变异，父母未见该变异。根据美国医学遗传学与基因组学学会变异相关指南，c.1720_1722delCTT评级为可能致病性变异(PS2＋PM2_Supporting＋PM4)。文献检索到13篇文献，HNRNPU基因变异类型有剪接点变异、无义变异、错义变异、框内缺失、基因重复、移码变异、多个外显子缺失。主要临床表现有发育迟缓、癫痫、智力低下、语言发育落后、颅面畸形、精神行为异常等。 结论 HNRNPU：c.1720_1722delCTT考虑为该NDDs患儿的致病原因。基因检测有助于儿童NDDs的诊断，变异发现丰富了HNRNPU基因变异致神经发育障碍基因变异谱。 Objective To explore the clinical characteristics and genetic variant in a child with neurodevelopmental disorders (NDDs). Methods Clinical data of a child who had presented at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology in December 2020 due to intermittent convulsions for over a year were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. " HNRNPU gene", "epilepsy", "epileptic encephalopathy", "hereditary epilepsy", "neurodevelopmental disorder", "neurodevelopmental syndrome", "HNRNPU", and "NDDs" were used as the key words to search the CNKI, Wanfang and PubMed databases dated from January 1, 1994 to February 10, 2022. Results The patient was a 2-year-old boy who had developed seizure at the age of 5 months. His clinical features had included abnormal appearance, recurrent seizures, and low developmental quotients of each functional area as evaluated by the Gesell scale. The child was given sodium valproate for the antiepileptic treatment and rehabilitation training. He had become seizure-free within half a year of follow-up, but his intelligence and motor development did not improve significantly. Genetic testing revealed that he has harbored a heterozygous c. 1720_1722delCTT (p.Lys574del) variant of the HNRNPU gene, which was not found in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2+ PM2_Supporting+ PM4). A total of 13 articles were retrieved, and the types of HNRNPU gene mutations have included splice site mutation, nonsense mutation, missense mutation, in-frame deletion, gene duplication, frameshifting mutation, and multiple exon deletion. The main clinical manifestations have included mental retardation, language delay, global developmental delay, epilepsy, craniofacial deformity, mental and behavioral abnormalities. Conclusion The c. 1720_1722delCTT variant of the HNRNPU gene probably underlay the NDDs in this child. Above finding has enriched the mutational spectrum of the HNRNPU gene.
Analysis of a child with neurodevelopmental disorders due to variant ofHNRNPU gene and a literature review
Objective To explore the clinical characteristics and genetic variant in a child with neurodevelopmental disorders (NDDs). Methods Clinical data of a child who had presented at Xiaogan Hospital Affiliated to Wuhan University of Science and Technology in December 2020 due to intermittent convulsions for over a year were retrospectively analyzed. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing. Candidate variants were verified by Sanger sequencing and bioinformatic analysis. " HNRNPU gene", "epilepsy", "epileptic encephalopathy", "hereditary epilepsy", "neurodevelopmental disorder", "neurodevelopmental syndrome", "HNRNPU", and "NDDs" were used as the key words to search the CNKI, Wanfang and PubMed databases dated from January 1, 1994 to February 10, 2022. Results The patient was a 2-year-old boy who had developed seizure at the age of 5 months. His clinical features had included abnormal appearance, recurrent seizures, and low developmental quotients of each functional area as evaluated by the Gesell scale. The child was given sodium valproate for the antiepileptic treatment and rehabilitation training. He had become seizure-free within half a year of follow-up, but his intelligence and motor development did not improve significantly. Genetic testing revealed that he has harbored a heterozygous c. 1720_1722delCTT (p.Lys574del) variant of the HNRNPU gene, which was not found in either of his parents. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS2+ PM2_Supporting+ PM4). A total of 13 articles were retrieved, and the types of HNRNPU gene mutations have included splice site mutation, nonsense mutation, missense mutation, in-frame deletion, gene duplication, frameshifting mutation, and multiple exon deletion. The main clinical manifestations have included mental retardation, language delay, global developmental delay, epilepsy, craniofacial deformity, mental and behavioral abnormalities. Conclusion The c. 1720_1722delCTT variant of the HNRNPU gene probably underlay the NDDs in this child. Above finding has enriched the mutational spectrum of the HNRNPU gene.
万方数据
