PDF(Pubmed)
Abstract：
Glycosylation is the most common protein and lipid post-translational modification in humans. Congenital disorders of glycosylation (CDG) are characterized by both genetic and clinical heterogeneity, presenting multisystemic manifestations, and in most cases are autosomal recessive in inheritance. The PIGN gene is responsible for the addition of phosphoethanolamine to the first mannose in the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, a highly conserved process that enables proteins to bind to the cell surface membrane. Here, we report a family with two siblings pediatric cases with the exact same compound heterozygous variants in PIGN. The (c.776T > C) variant of uncertain significance (VUS) together with a known pathogenic variant (c.932T > G), resulting in clinical features compatible with PIGN-related conditions, more specific the CDG. This is the first time that PIGN variant c.776T > C is reported in literature in individuals with PIGN-congenital disorder of glycosylation (PIGN-CDG), and the current submission in ClinVar by Invitae® is specifically of our case. Detailed clinical information and molecular analyses are presented. Here, we show for the first time two affected siblings with one pathogenic variant (c.932T > G) and the c.776T > C VUS in trans. In honor of the family, we propose the name Bella-Noah Syndrome for disorder.
摘要：
糖基化是人类中最常见的蛋白质和脂质翻译后修饰。先天性糖基化疾病（CDG）的特点是遗传和临床异质性。呈现多系统表现，在大多数情况下是常染色体隐性遗传。PIGN基因负责向糖基磷脂酰肌醇（GPI）-锚生物合成途径中的第一个甘露糖添加磷酸乙醇胺，一个高度保守的过程，使蛋白质结合到细胞表面膜。这里,我们报告了一个有两个兄弟姐妹的儿科病例的家庭，在PIGN中具有完全相同的复合杂合变体。（c.776T>C）具有不确定意义（VUS）的变体以及已知的致病性变体（c.932T>G），导致与PIGN相关病症相容的临床特征，更具体的CDG。这是文献中首次报道PIGN变异c.776T>C在患有PIGN先天性糖基化障碍（PIGN-CDG）的个体中，Invitae®目前在ClinVar提交的文件专门针对我们的案例。提供了详细的临床信息和分子分析。这里,我们首次显示了两个受影响的兄弟姐妹，它们具有一个致病变体（c.932T>G）和反式的c.776T>CVUS。为了纪念这个家庭，我们建议用贝拉-诺亚综合症来治疗疾病.
