Analysis of clinical phenotype and gene variation of a child with neurodevelopmental disorder caused by homozygous variation of TRAPPC6B gene
10.3760/cma.j.cn511374-20240918-00497
- VernacularTitle: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
- Author:
Wenxia LI
1
;
Yuke LI
;
Baiyun CHEN
;
Weimeng LI
;
Xiaoman ZHANG
;
Linfei LI
;
Qing SHANG
Author Information
1. 郑州大学附属儿童医院，河南省儿童医院郑州儿童医院康复医学科，郑州 450018
- Publication Type:Journal Article
- Keywords:
Neurodevelopmental disorders;
TRAPPC6B gene;
Homozygous variation;
Inbreeding;
Child development disorders, pervasive;
Child
- From:
Chinese Journal of Medical Genetics
2025;42(2):170-174
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To 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. Methods:A 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). Results:The 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. Conclusion:The 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.
