The Central Laboratory of Birth Defects Prevention and Control, Ningbo Women and Children's Hospital, Ningbo, Zhejiang 315012, China.
Department of Laboratory Medicine of Kunming Children's Hospital, Key Laboratory of Child Critical Disease Research of Yunnan Province, Kunming, Yunnan 650034, China.
Biomed Res Int. 2021 Feb 11;2021:6661860. doi: 10.1155/2021/6661860. eCollection 2021.
PPP2R5D-related neurodevelopmental disorder, which is mainly caused by de novo missense variants in the gene, is a rare autosomal dominant genetic disorder with about 100 patients and a total of thirteen pathogenic variants known to exist globally so far. Here, we present a 24-month-old Chinese boy with developmental delay and other common clinical characteristics of PPP2R5D-related neurodevelopmental disorder including hypotonia, macrocephaly, intellectual disability, speech impairment, and behavioral abnormality. Trio-whole exome sequencing (WES) and Sanger sequencing were performed to identify the causal gene variant. The pathogenicity of the variant was evaluated using bioinformatics tools. We identified a novel pathogenic variant in the gene (c.620G>T, p.Trp207Leu). The variant is located in the variant hotspot region of this gene and is predicted to cause PPP2R5D protein dysfunction due to an increase in local hydrophobicity and unstable three-dimensional structure. We report a novel pathogenic variant of associated with PPP2R5D-related neurodevelopmental disorder from a Chinese family. Our findings expanded the phenotypic and mutational spectrum of PPP2R5D-related neurodevelopmental disorder.
PPP2R5D 相关性神经发育障碍主要由该基因中的新生错义变异引起，是一种罕见的常染色体显性遗传疾病，全球目前已知约有 100 名患者，存在总计 13 种致病性变异。在此，我们报告了一例 24 月龄的中国男孩，其具有发育迟缓以及 PPP2R5D 相关性神经发育障碍的其他常见临床特征，包括张力减退、大头畸形、智力残疾、言语障碍和行为异常。对先证者及其父母进行了 trio-whole 外显子组测序（WES）和 Sanger 测序，以鉴定致病基因突变。使用生物信息学工具评估变异的致病性。我们在 基因中发现了一个新的致病性变异（c.620G>T，p.Trp207Leu）。该变异位于该基因的变异热点区域，由于局部疏水性增加和不稳定的三维结构，预计会导致 PPP2R5D 蛋白功能障碍。我们从一个中国家系中报道了一个与 PPP2R5D 相关性神经发育障碍相关的 基因的新型致病性变异。我们的发现扩展了 PPP2R5D 相关性神经发育障碍的表型和突变谱。
