■5岁以下儿童发育迟缓,全球发病率为10%-15%,是由包括遗传在内的多种因素引起的,产前条件,围产期并发症,产后影响,社会因素,和营养缺乏。诸如EFNB1,MECP2和TRAPPC9之类的基因变体在蛋白质变形和核因子κB(NF-κB)活性的下调中起着重要作用。
■一个3岁的女孩,表现出糟糕的运动技能,个人社会发展,听觉语言,手眼协调,和视觉表现,被诊断为全球发育迟缓。进行了Trio全外显子组测序以确定其病情的遗传病因。然后通过Sanger测序和定量聚合酶链反应(qPCR)验证鉴定的遗传病因。
■遗传分析显示患者在TRAPPC9基因中具有复合杂合变体。其中包括从未受影响的父亲继承的c.1928del移码变体和从未受影响的母亲继承的外显子12中的缺失。根据美国医学遗传学学院(ACMG)的指南,这些变异被归类为“可能致病”。
■研究表明,复合杂合TRAPPC9基因变异体可导致中国女孩的发育迟缓。根据ACMG标准,这些变体已被分类为具有显着的致病作用,提示隐性遗传模式,并强调产前检查对未来后代的重要性。此外,我们的发现扩大了TRAPPC9基因的基因型谱,并为经历发育迟缓的儿童提供更全面的遗传咨询信息。
UNASSIGNED: 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 EFNB1, MECP2 and TRAPPC9 play a significant role in protein deformation and downregulation of nuclear factor κB (NF-κB) activity.
UNASSIGNED: 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).
UNASSIGNED: Genetic analysis revealed that the patient had compound heterozygous variants in the TRAPPC9 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\".
UNASSIGNED: 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.