目的探讨1例 TRAPPC6B基因纯合移码变异所致神经发育障碍患儿的临床表型和基因变异情况，为该病诊断提供参考。
方法选择因"1岁3个月不会独立站立、行走"，2023年3月于郑州大学附属儿童医院就诊的1例 TRAPPC6B基因纯合变异所致神经发育障碍患儿作为研究对象。采用回顾性研究方法，收集患儿相关临床资料。采集患儿及其父母外周血样，应用目标捕获高通量测序对患儿及其父母进行基因变异检测。对患儿检出的候选变异，采用Sanger测序法对患儿及其父母进行验证，并进行生物信息学分析。根据美国医学遗传学与基因组学学会(ACMG)制定的《遗传变异分类标准与指南》(以下简称为"ACMG指南")，对该变异进行致病性评级。本研究已通过郑州大学附属儿童医院伦理委员会审查(批准号：2022-K-L025)。
结果患儿为1岁3个月男性，其父母为近亲婚配。患儿表现为全面发育落后、小头畸形、身材矮小。头颅MRI显示，患儿白质髓鞘化发育落后、双侧侧脑室周围白质及双侧外囊异常信号、胼胝体细薄、第三脑室增宽。基因检测结果提示，患儿 TRAPPC6B基因存在c.240_241delAA(p.Q80Hfs*34)纯合移码变异，遗传自其父母。根据ACMG指南，该变异被评定为可能致病性(PVS1_Strong＋PM2_Supporting＋PM3_Supporting)。该变异导致编码蛋白的终止密码子提前出现，蛋白三维结构发生改变。该变异位点位于TRAPPC6B蛋白功能结构域，可能直接影响蛋白质功能域，导致功能域缺陷。
结论 TRAPPC6B基因c.240_241delAA(p.Q80Hfs*34)移码变异既往未见报道，这可能是该研究神经发育障碍患儿的遗传致病原因。上述发现拓展了 TRAPPC6B基因变异谱，为该病家系遗传咨询及产前诊断提供依据。
ObjectiveTo explore the clinical phenotype and genetic characteristics of a child with neurodevelopmental disorder caused by homozygous frameshift variant of the TRAPPC6B gene, and to provide reference for the diagnosis of the disease.
MethodsA child with neurodevelopmental disorder caused by homozygous variant of TRAPPC6B gene who was admitted to the Children′s Hospital Affiliated to Zhengzhou University in March 2023 due to " inability to stand and walk independently at 1 year and 3 months old" was selected as the study object. The clinical data were collected by retrospective analysis method. Target region high-throughput sequencing was carried out on the child and parental peripheral blood samples, and candidate variant was verified by Sanger sequencing and bioinformatic analysis. The pathogenicity of variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by American College of Medical Genetics and Genomics (ACMG) (hereinafter referred to as ACMG guidelines). The study has been approved by the Medical Ethics Committee of the Children′s Hospital Affiliated to Zhengzhou University (Ethics No.2022-K-L025).
ResultsThe child was a 1-year-and-3-months-old boy whose parents were sib mating. The child presented with global developmental delay, microcephaly and short stature. MRI showed poor white matter myelination, abnormal signals of bilateral periventricular white matter and bilateral external sac, thin corpus callosum, and widening of the third ventricle. Genetic testing revealed that the TRAPPC6B gene of the child had a homozygous variant of c. 240_241delAA (p.Q80Hfs*34), which was inherited from his parents. According to the ACMG guidelines, this variant was judged to be potentially pathogenic (PVS1_Strong+ PM2_Supporting+ PM3_Supporting), resulting in premature occurrence of terminator codons and a change in the three-dimensional structure of protein. The variant was located in the functional domain, which may directly affect the functional domain of the protein, resulting in functional domain defects.
ConclusionThe frameshift variation of TRAPPC6B gene c. 240_241delAA (p.Q80Hfs*34) has not been reported, which may be the genetic cause of neurodevelopmental disorders in child in this study. These findings expand the variation spectrum of TRAPPC6B gene and provid basis for genetic counseling and prenatal diagnosis of this family.
李文霞,李雨珂,陈白云,等. TRAPPC6B基因纯合变异所致神经发育障碍患儿1例的临床表型和基因变异分析 [J]. 中华医学遗传学杂志,2025,42(02)：170-174.
DOI:10.3760/cma.j.cn511374-20240918-00497版权归中华医学会所有。
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除非特别声明，本刊刊出的所有文章不代表中华医学会和本刊编委会的观点。
李文霞：实验设计、论文撰写；李雨珂：数据收集、统计分析；陈白云：临床诊治、遗传咨询；李尉萌：数据收集、遗传咨询；张小慢：二代测序实验、生物信息学分析；李林飞：指导研究、论文修改；尚清：指导研究、经费支持
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