Familial SYN1 Pathogenic Mutations Related Neurodevelopmental Disorders in Asian Pediatric Patients

Abstract

Background: SYN1 encodes synapsin I, which is a neuronal phosphoprotein in relation to the membranes of small synaptic vesicles. Pathogenic variants in the gene have been confirmed as genetic causes of neurodevelopmental disorders. Methods: In our study, we collected clinical information of two male probands with intellectual disability, and performed whole exome sequencing on both patients and their parents. We also reviewed more SYN1 variant cases in pervious publications.Results: Two maternally inherited variants in SYN1 gene (NM_133499:c.C1076A (p.T359K) in proband A and NM_133499:c.C1444T (p. Q482X) in proband B) were found in our patients, which have never been described in detail before. After a literature review, we found that all probands have been reported so far were male, who inherited the significant SYN1 variants from their asymptomatic or mild affected mother. Although the disease encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, the phenotypes of family members vary in gender.Conclusion: Here, we firstly report two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Our results supported that gender and phenotype differences should be highly valued in this disorder.