SPOUT1 variants associated with autosomal-recessive developmental and epileptic encephalopathy

作者：Wenwei Liu, Kai Gao, Xilong Du, Sijia Wen, Huifang Yan, Jingmin Wang, Yong Wang, Conglei Song, Lin Li, Taoyun Ji, Weiyue Gu, Yuwu Jiang · 发表于：Acta Epileptologica · 年份：2024 · DOI：10.1186/s42494-024-00185-0 · 被引用次数：5 · 研究领域：Genomics and Rare Diseases、Microtubule and mitosis dynamics、Genetic and Kidney Cyst Diseases

BACKGROUND: Developmental and epileptic encephalopathy (DEE) is a group of neurodevelopmental disorders characterized by early-onset seizures predominantly attributed to genetic causes. Nevertheless, numerous patients remain without identification of a genetic cause. METHODS: We present four unrelated Chinese patients with SPOUT1 compound heterozygous variants, all of whom were diagnosed with DEE. We also investigated functions of SPOUT1 using the spout1 knockout zebrafish model. RESULTS: The four unrelated DEE patients with SPOUT1 compound heterozygous variants were all males. Their onset age of seizure ranged from 3 months to 6 months (median age 5 months). All patients had epileptic spasms, and were diagnosed with infantile epileptic spasms syndrome (IESS). Three patients had microcephaly during infancy. Brain MRI in three patients showed white matter hypomyelination and bilaterally widened frontotemporal subarachnoid space. At the last follow-up, two patients exhibited drug-resistant epilepsy, one achieved seizure freedom following vigabatrin treatment, and one died at the age of 4 years and 5 months from probable sudden unexpected death in epilepsy. Seven different SPOUT1 variants were identified in the four patients, including six missense variants and one deletion variant. AlphaFold2 prediction indicated that all variants alternated the number or the length of bonds between animo acids in protein SPOUT1. Neurophysiological results from spout1 knockout zebrafish reveale...