Identification ofNONO gene variant in a child with congenital heart disease and global developmental delay
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目的 探讨1例先天性心脏病(CHD)伴全面发育迟缓(GDD)患儿的遗传学病因。 方法 选取2022年4月27日于福建省儿童医院心脏外科就诊的1例CHD伴GDD患儿为研究对象。收集患儿的临床资料，采集患儿的脐带血样及其父母的外周静脉血样，用全外显子组测序(WES)对患儿进行检测，对候选变异进行Sanger测序家系验证，并分析其致病性。 结果 患儿为男性，3岁3个月，具有心脏异常及发育迟缓等表现。WES检测结果提示其NONO基因存在c.457C>T(p.Arg153*)无义变异，Sanger测序证实其父母均未携带相同的变异。该变异已被在线人类孟德尔遗传(OMIM)、美国国家生物技术信息中心临床突变数据库(ClinVar)及人类基因突变数据库(HGMD)收录；而未被国际千人基因组计划数据库(1000 Genomes)、单核苷酸多态性数据库(dbSNP)和基因组聚合数据库(gnomAD)等正常人群数据库收录。根据美国医学遗传学与基因组学学会(ACMG)相关指南评级为致病性变异。 结论 NONO基因c.457C>T(p.Arg153*)变异可能是本研究CHD伴全面发育迟缓患儿的遗传学病因。上述发现丰富了NONO基因c.457C>T(p.Arg153*)变异的表型谱，为患儿的临床诊断与家系遗传咨询提供了依据。 Objective To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). Methods A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children′s Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c. 457C>T(p.Arg153*) in theNONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. Conclusion The c. 457C>T(p.Arg153*) variant of theNONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
Objective To explore the genetic basis for a child with congenital heart disease (CHD) and global developmental delay (GDD). Methods A child who was hospitalized at the Department of Cardiac Surgery of Fujian Children′s Hospital on April 27, 2022 was selected as the study subject. Clinical data of the child was collected. Umbilical cord blood sample of the child and peripheral blood samples of his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Results The child, a 3-year-and-3-month-old boy, had manifested cardiac abnormalities and developmental delay. WES revealed that he had harbored a nonsense variant of c. 457C>T(p.Arg153*) in theNONO gene. Sanger sequencing showed that neither of his parents has carried the same variant. The variant has been recorded by the OMIM, ClinVar and HGMD databases, but not in the normal population databases of 1000 Genomes, dbSNP and gnomAD. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was rated as a pathogenic variant. Conclusion The c. 457C>T(p.Arg153*) variant of theNONO gene probably underlay the CHD and GDD in this child. Above finding has expanded the phenotypic spectrum of the NONO gene and provided a reference for the clinical diagnosis and genetic counseling for this family.
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