Identification of a novel homozygous SLC13A5 nonstop mutation in a Chinese family with epileptic encephalopathy and developmental delay

Hua He ¹ Lijuan Long ² Man-ling Tang ¹ Qiang Xu ³ Shengwu Duan ⁴ Ge Chen ⁵ Yan Zhao ³ Qiongfang Wu ³ Jia Chen ^3*

• ¹ Laboratory Medicine Center, Zhuzhou Hospital affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China
• ² Department of Critical Care Medicine, Zhuzhou Hospital affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China
• ³ Reproductive Medicine Center, Jiangxi Maternal and Child Health Hospital, Nanchang, China
• ⁴ Department of Radiology, Zhuzhou Hospital affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China
• ⁵ Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, China

Introduction: Biallelic loss-of-function variants in the SLC13A5 (solute carrier family 13, member 5) gene are responsible for autosomal recessive developmental and epileptic encephalopathy 25 with amelogenesis imperfecta (DEE25). Until now, no pathogenic variants of SLC13A5 has been reported among the Chinese population.Methods: A Chinese Han pediatric patient with epilepsy and global developmental delay was described in this study. Trio-whole exome sequencing (WES) including the patient and her parents was performed to determine the genetic basis of the phenotype. Potential pathogenic variants were subsequently confirmed by Sanger sequencing. Additionally, we conducted an extensive review of the literature regarding SLC13A5 variants to analyze their associated phenotypic characteristics.Results: Trio-WES revealed a novel homozygous variant c.1705T>G in SLC13A5 associated with clinical manifestations in the proband. The variant was also detected in her parents and unaffected sister, who were both heterozygous carriers. The variant is a nonstop substitution that is predicted to extend the SLC13A5 protein by 174 amino acids (p.569Gluext174). Immunofluorescence analysis showed that the p.569Gluext174 mutant protein is stably expressed and does not affect the subcellular localization of SLC13A5 in HEK293 cells. Furthermore, analysis Analysis of previously published cases indicated that SLC13A5 patient in our study exhibited overlapping symptoms.