Abstract：
ALG9-CDG is a CDG-I defect within the group of Congenital Disorders of Glycosylation (CDG). We here describe the clinical symptoms of two new and unrelated ALG9-CDG patients, both carrying the novel homozygous missense variant c.1460 T > C (p.L487P) in the ALG9 gene which led to global developmental delay, psychomotor disability, facial dysmorphisms, brain and heart defects, hearing loss, hypotonia, as well as feeding problems. New clinical symptoms comprised West syndrome with hypsarrhythmia. Quantitative RT-PCR analysis revealed a significantly enhanced ALG9 mRNA transcript level, whereas the protein amount in fibroblasts was significantly reduced. This could be ascribed to a stronger degradation of the mutated ALG9 protein in patient fibroblasts. Lipid-linked oligosaccharide analysis showed an ALG9-CDG characteristic accumulation of Man6GlcNAc2-PP-dolichol and Man8GlcNAc2-PP-dolichol in patient cells. The clinical findings of our patients and of all previously published ALG9-CDG patients are brought together to further expand the knowledge about this rare N-glycosylation disorder. SYNOPSIS: Homozygosity for p.L487P in ALG9 causes protein degradation and leads to West syndrome.
摘要：
ALG9-CDG是先天性糖基化障碍(CDG)内的CDG-I缺陷。我们在这里描述了两个新的和无关的ALG9-CDG患者的临床症状，两者都携带新的纯合错义变体c.1460T>C（p。L487P）在ALG9基因中导致整体发育迟缓，精神运动障碍，面部畸形，大脑和心脏缺陷,听力损失,低张力,以及喂养问题。新的临床症状包括伴有心律失常的West综合征。定量RT-PCR分析显示ALG9mRNA转录水平显着增强，而成纤维细胞中的蛋白质含量显着减少。这可以归因于患者成纤维细胞中突变的ALG9蛋白的更强降解。脂质连接的寡糖分析显示Man6GlcNAc2-PP-dolicol和Man8GlcNAc2-PP-dolicol在患者细胞中的ALG9-CDG特征性积累。将我们的患者和所有先前发表的ALG9-CDG患者的临床发现汇集在一起，以进一步扩大对这种罕见的N-糖基化疾病的认识。简介：ALG9中p.L487P的纯合性导致蛋白质降解并导致West综合征。
