The Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Henan Engineering Research Center for Gene Editing of Human Genetic Disease, Jianshe Rd, Erqi District, Zhengzhou, Henan, 450052, People's Republic of China.
Henan Provincial Key Laboratory of Children's Genetics and Metabolic Diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou Children's Hospital, No-33, Longhu Waihuan East Road, 450018, Zhengzhou, Henan Province, China.
Eur J Med Genet. 2021 Jan;64(1):104101. doi: 10.1016/j.ejmg.2020.104101. Epub 2020 Nov 12.
N-ethylmaleimide-sensitive factor attachment proteins (NAP: NAPA and NAPB) play a role in Soluble N-ethylmaleimide-sensitive accessory protein receptor (SNARE) complex dissociation and recycling, associated with neuronal regulation and brain development and various severe early-onset epilepsies. Here, we report two patients from a Chinese family presenting with unexplained early-onset epileptic encephalopathies (EOEE) syndrome characterized by multifocal seizures, profound intellectual disability and global developmental delay. We identified the homozygous c.433-1G > A variant of the NAPB as the causative by trio-based exome sequencing. The novel splicing mutation in NAPB was third variant reported associated with EOEE syndrome. Our results gave further hints on the associations of variants in NAPB with EOEE and indicated that for patients with unexplained EOEE, the NAPB gene should be included into the data analysis from whole exome sequencing, which contributes to uncover more patients affected and rich the phenotypic spectrum.
N-乙基马来酰亚胺敏感因子附着蛋白（NAP：NAPA 和 NAPB）在可溶性 N-乙基马来酰亚胺敏感辅助蛋白受体（SNARE）复合物解离和再循环中发挥作用，与神经元调节和大脑发育以及各种严重的早发性癫痫有关。在这里，我们报告了来自一个中国家庭的两名患者，他们表现出不明原因的早发性癫痫性脑病（EOEE）综合征，其特征是多灶性发作、严重的智力残疾和全面发育迟缓。我们通过基于三人组的外显子组测序鉴定了 NAPB 的纯合 c.433-1G>A 变体为致病原因。该新的剪接突变是与 EOEE 综合征相关的第三个报道的 NAPB 变异。我们的结果进一步提示了 NAPB 基因变异与 EOEE 的相关性，并表明对于不明原因的 EOEE 患者，应将 NAPB 基因纳入全外显子组测序的数据分析中，这有助于发现更多受影响的患者并丰富表型谱。
