Pan Yijun, Ren Bin, Chen Lijuan, Li Qiang
Department of Pediatric Neurology, Guiyang Maternal and Child Health Care Hospital, Guiyang, China.
Department of Genetic Counseling, Shanghai Nyuen Biotechnology Co., Ltd., Shanghai, China.
Front Pediatr. 2024 Dec 2;12:1419976. doi: 10.3389/fped.2024.1419976. eCollection 2024.
Recently, mutations have been identified in six genes (, , , , and ) encoding proteins in the Glycosyl phosphatidylinositol(GPI)-anchor-synthesis pathway in individuals with hyperphosphatasia with impaired intellectual development syndrome(HPMRS). Reports involving the rare pathogenic gene, post-GPI attachment to proteins 2 () are quite limited. In this study, we reported two patients with variants related neurodevelopmental disorders from Asian population. The proband, onset of epileptic spasms at 5 months, concurrently with global developmental dalay, facial malformation and elevated alkaline phosphatase. His younger sister, onset of epileptic spasms at 2 months, having similar clinical features as the proband. Their phenotypes are consistent with related diseases. The two missense variants [c.686C>T (p.Ala229Val) and c.677C>T (p.Thr226Ile)] in gene found in this family were segregation with the disease, while c.677C>T (p.Thr226Ile) was a novel variant. All the two patients showed a positive response to ACTH treatment and high-dose pyridoxine. In summary, this study contributes to expanding the pathogenic variant spectrum of related HPMRS, and provides new insights into the treatment.
最近，在患有智力发育障碍综合征（HPMRS）的高磷酸酶血症患者中，已在糖基磷脂酰肌醇（GPI）锚合成途径中编码蛋白质的六个基因（、、、、和）中鉴定出突变。涉及罕见致病基因——蛋白质GPI后附着蛋白2（）的报道非常有限。在本研究中，我们报告了两名来自亚洲人群的携带与神经发育障碍相关的变体的患者。先证者在5个月时出现癫痫痉挛，同时伴有全面发育迟缓、面部畸形和碱性磷酸酶升高。他的妹妹在2个月时出现癫痫痉挛，具有与先证者相似的临床特征。他们的表型与相关疾病一致。在这个家族中发现的基因中的两个错义变体[c.686C>T（p.Ala229Val）和c.677C>T（p.Thr226Ile）]与疾病共分离，而c.677C>T（p.Thr226Ile）是一个新变体。两名患者对促肾上腺皮质激素治疗和高剂量吡哆醇均表现出阳性反应。总之，本研究有助于扩大相关HPMRS的致病变体谱，并为治疗提供新的见解。
