Skip to main content

CASE REPORT article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1415194

Whole Exome Sequencing Identifies Compound Heterozygous Variants in the TRAPPC9 Gene in a Child with Developmental Delay

Provisionally accepted
Bingxuan Yu Bingxuan Yu 1,2Jing Chen Jing Chen 2Shuo Yang Shuo Yang 2He Wang He Wang 2Yuanyuan Xiao Yuanyuan Xiao 2*Shanling Liu Shanling Liu 2
  • 1 Sichuan University, Chengdu, China
  • 2 West China Second University Hospital, Sichuan University, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Background: Developmental delay (DD) in children under 5 years old, which occurs globally with an incidence of 10% to 15%, is caused by multiple factors including genetics, prenatal conditions, perinatal complications, postnatal influences, social factors, and nutritional deficiencies. Gene variants such as EFNB1, MECP2 and TRAPPC9 play a significant role in protein deformation and downregulation of nuclear factor κB (NF-κB) activity. Methods: A 3-year-old girl, who exhibits poor gross motor skills, personal-social development, auditory language, hand-eye coordination, and visual performance, was diagnosed with global developmental delay (GDD). Trio whole exome sequencing was conducted to identify the genetic etiology of her condition. The identified genetic etiology was then validated through Sanger sequencing and quantitative polymerase chain reaction (qPCR). Results: Genetic analysis revealed that the patient had compound heterozygous variants in the TRAPPC9 gene. Both variants were not reported in other studies. These include a novel c.1928del frameshift variant inherited from the unaffected father and a deletion in exon 12 inherited from the unaffected mother. According to the American College of Medical Genetics (ACMG) guidelines, these variants were classified as "likely pathogenic".The study revealed that compound heterozygous TRAPPC9 gene variants cause developmental delay in a Chinese girl. These variants have been classified as having significant pathogenic effect according to the ACMG criteria, suggesting a recessive genetic pattern and highlighting the importance of prenatal testing for future offspring. Furthermore, our findings expand the genotype spectrum of the TRAPPC9 gene, and provide more comprehensive information regarding genetic counseling for children experiencing developmental delay.

    Keywords: developmental delay, TRAPPC9, variants, whole exome sequencing, Frame shift

    Received: 10 Apr 2024; Accepted: 29 Jul 2024.

    Copyright: © 2024 Yu, Chen, Yang, Wang, Xiao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Yuanyuan Xiao, West China Second University Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.