Department of Rehabilitation, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cipher Gene, LLC, Beijing, China.
Cytogenet Genome Res. 2021;161(10-11):514-519. doi: 10.1159/000520296. Epub 2021 Dec 8.
Recently, an increasing number of genes have been associated with global developmental delay (GDD) and intellectual disability (ID). The sorting nexin (SNX) protein family plays multiple roles in protein trafficking and intracellular signaling. SNXs have been reported to be associated with several disorders, including Alzheimer disease and Down syndrome. Despite the growing evidence of an association of SNXs with neurodegeneration, SNX13 deficiency has not been associated with GDD or ID. In this study, we present the case of a 4-year-old boy with brain dysplasia and GDD, including language delay, cognitive delay, and dyskinesia. Exome sequencing revealed a 1-bp homozygous deletion in SNX13 (NM_015132.5: exon8: c.742_743del; p.Tyr248Leufs*20), which caused a frameshift and predicted early termination. Sanger sequencing confirmed that the variant was inherited from his parents respectively. Our findings associate SNX13 variation with GDD for the first time and provide a new GDD candidate gene.
最近，越来越多的基因与全面发育迟缓（GDD）和智力障碍（ID）有关。分选连接蛋白（SNX）蛋白家族在蛋白质运输和细胞内信号转导中发挥多种作用。已经有报道称 SNXs 与多种疾病有关，包括阿尔茨海默病和唐氏综合征。尽管越来越多的证据表明 SNXs 与神经退行性变有关，但 SNX13 的缺乏与 GDD 或 ID 无关。在这项研究中，我们报告了一例 4 岁男孩，患有脑发育不良和 GDD，包括语言延迟、认知延迟和运动障碍。外显子组测序显示 SNX13 存在 1 个碱基的纯合缺失（NM_015132.5:exon8:c.742_743del;p.Tyr248Leufs*20），导致移码和提前终止。Sanger 测序证实该变异分别从父母遗传而来。我们的研究结果首次将 SNX13 的变异与 GDD 联系起来，并为 GDD 提供了一个新的候选基因。
