Hu Wenjing, Fang Hongjun, Tang Jingwen, Zhou Zhen, Wu Liwen
Department of Neurology, Hunan Children's Hospital, Changsha, Hunan 410007, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2023 Apr 10;40(4):385-389. doi: 10.3760/cma.j.cn511374-20221206-00844.
To explore the clinical phenotype and genetic basis of a child with early onset neurodevelopmental disorder with involuntary movement (NEDIM).
A child who presented at Department of Neurology of Hunan Children's Hospital on October 8, 2020 was selected as the study subject. Clinical data of the child were collected. Genomic DNA was extracted from peripheral blood samples of the child and his parents. Whole exome sequencing (WES) was carried out for the child. Candidate variant was verified by Sanger sequencing and bioinformatic analysis. Relevant literature was searched from the CNKI, PubMed and Google Scholar databases to summarize the clinical phenotypes and genetic variants of the patients.
This child was a 3-year-and-3-month boy with involuntary trembling of limbs and motor and language delay. WES revealed that the child has harbored a c.626G>A (p.Arg209His) variant of the GNAO1 gene. Sanger sequencing confirmed that neither of his parents has carried the same variant. The variant had been reported in HGMD and ClinVar databases, but not in the dbSNP, ExAC and 1000 Genomes databases. Prediction with SIFT, PolyPhen-2, and Mutation Taster online software suggested that the variant may be deleterious to the protein function. By UniProt database analysis, the encode amino acid is highly conserved among various species. Prediction with Modeller and PyMOL software indicated that the variant may affect the function of GαO protein. Based on the guideline of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic.
The GNAO1 gene c.626G>A (p.Arg209His) variant probably underlay the NEDIM in this child. Above finding has expanded the phenotypic spectrum of GNAO1 gene c.626G>A (p.Arg209His) variant and provided a reference for clinical diagnosis and genetic counseling.
探讨一名患有早发性神经发育障碍伴不自主运动（NEDIM）儿童的临床表型及遗传基础。
选取2020年10月8日就诊于湖南省儿童医院神经内科的一名儿童作为研究对象。收集该儿童的临床资料。从该儿童及其父母的外周血样本中提取基因组DNA。对该儿童进行全外显子组测序（WES）。通过Sanger测序和生物信息学分析验证候选变异。从中国知网、PubMed和谷歌学术数据库检索相关文献，总结患者的临床表型和遗传变异。
该儿童为3岁3个月男孩，有肢体不自主震颤及运动和语言发育迟缓。WES显示该儿童携带GNAO1基因的c.626G>A（p.Arg209His）变异。Sanger测序证实其父母均未携带相同变异。该变异已在HGMD和ClinVar数据库中报道，但未在dbSNP、ExAC和千人基因组数据库中报道。使用SIFT、PolyPhen-2和Mutation Taster在线软件预测表明该变异可能对蛋白质功能有害。通过UniProt数据库分析，编码氨基酸在不同物种间高度保守。使用Modeller和PyMOL软件预测表明该变异可能影响GαO蛋白的功能。根据美国医学遗传学与基因组学学会（ACMG）的指南，该变异被评为致病变异。
GNAO1基因c.626G>A（p.Arg209His）变异可能是该儿童NEDIM的病因。上述发现扩展了GNAO1基因c.626G>A（p.Arg209His）变异的表型谱，为临床诊断和遗传咨询提供了参考。
