Yu Bingxuan, Chen Jing, Yang Shuo, Wang He, Xiao Yuanyuan, Liu Shanling
Department of Medical Genetics/Prenatal Diagnostic Center, West China Second University Hospital, Sichuan University, Chengdu, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, China.
Front Genet. 2024 Aug 9;15:1415194. doi: 10.3389/fgene.2024.1415194. eCollection 2024.
Developmental delay in children under 5 years old, which occurs globally with an incidence of 10%-15%, is caused by multiple factors including genetics, prenatal conditions, perinatal complications, postnatal influences, social factors, and nutritional deficiencies. Gene variants such as , and play a significant role in protein deformation and downregulation of nuclear factor κB (NF-κB) activity.
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. 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).
Genetic analysis revealed that the patient had compound heterozygous variants in the gene. These include a 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 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 gene, and provide more comprehensive information regarding genetic counseling for children experiencing developmental delay.
全球5岁以下儿童发育迟缓的发生率为10%-15%，由多种因素引起，包括遗传、产前状况、围产期并发症、产后影响、社会因素和营养缺乏。基因变异如 、 和 在蛋白质变形和核因子κB（NF-κB）活性下调中起重要作用。
一名3岁女孩表现出粗大运动技能、个人社交发展、听觉语言、手眼协调和视觉表现较差，被诊断为全面发育迟缓。进行了三联体全外显子组测序以确定其病情的遗传病因。然后通过桑格测序和定量聚合酶链反应（qPCR）对确定的遗传病因进行验证。
基因分析显示该患者在 基因中有复合杂合变异。这些变异包括从未受影响的父亲遗传的c.1928del移码变异和从未受影响的母亲遗传的外显子12缺失。根据美国医学遗传学学院（ACMG）指南，这些变异被分类为“可能致病”。
该研究揭示了复合杂合 基因变异导致一名中国女孩发育迟缓。根据ACMG标准，这些变异被分类为具有显著致病作用，提示隐性遗传模式，并突出了对未来后代进行产前检测的重要性。此外，我们的发现扩展了 基因的基因型谱，并为发育迟缓儿童的遗传咨询提供了更全面的信息。
