先天性糖基化障碍(CDG)是指以导致多器官障碍的蛋白质或脂质的糖基化缺陷为特征的单基因疾病。这里,我们研究了SSR4-CDG的临床特征和遗传变异,并对其发病机制进行了初步研究。
■我们回顾性报道1例男性早期呼吸窘迫患儿的临床资料,先天性膈膨出,美容畸形,和中等生长迟缓。从病例和家长身上采集外周血,提取基因组DNA并进行全外显子组测序.通过实时定量PCR定量SSR4基因的mRNA表达。随后对病例和健康儿童进行RNA测序分析。
■对该病例及其父母的基因组DNA进行全外显子组测序,结合该病例的临床特征,确定了SSR4中的半合子c.80_96del,最终考虑了CDG的诊断。在这种情况下,SSR4的表达下调。该病例存在1,078个基因下调和536个基因上调。SSR4基因表达在此情形下显著下调。同时,基因集富集分析(GSEA)显示SSR4-CDG可能影响止血,凝血,分解代谢,红细胞发育和稳态调节,肌肉收缩和调节,等。高热量配方喂养和康复训练后生长迟缓的改善。
■我们的研究扩展了SSR4-CDG变异谱和临床表型,并分析了可能受SSR4-CDG影响的通路,这可能提供对SSR4功能的进一步见解,并帮助临床医生更好地了解这种疾病。
UNASSIGNED: Congenital disorders of glycosylation (CDG) refer to monogenetic diseases characterized by defective glycosylation of proteins or lipids causing multi-organ disorders. Here, we investigate the clinical features and genetic variants of SSR4-CDG and conduct a preliminary investigation of its pathogenesis.
UNASSIGNED: We retrospectively report the clinical data of a male infant with early life respiratory distress, congenital diaphragmatic eventration, cosmetic deformities, and moderate growth retardation. Peripheral blood was collected from the case and parents, genomic DNA was extracted and whole-exome sequencing was performed. The mRNA expression of SSR4 gene was quantified by Real-time Quantitative PCR. RNA sequencing analysis was subsequently performed on the case and a healthy child.
UNASSIGNED: Whole-exome sequencing of the case and his parents\' genomic DNA identified a hemizygous c.80_96del in SSR4, combined with the case\'s clinical features, the diagnosis of CDG was finally considered. In this case, the expression of SSR4 was downregulated. The case were present with 1,078 genes downregulated and 536 genes upregulated. SSR4 gene expression was significantly downregulated in the case. Meanwhile, gene set enrichment analysis (GSEA) revealed that SSR4-CDG may affect hemostasis, coagulation, catabolism, erythrocyte development and homeostatic regulation, and muscle contraction and regulation, etc. Improvement of growth retardation in case after high calorie formula feeding and rehabilitation training.
UNASSIGNED: Our study expanded the SSR4-CDG variant spectrum and clinical phenotype and analyzed pathways potentially affected by SSR4-CDG, which may provide further insights into the function of SSR4 and help clinicians better understand this disorder.