Abstract
BackgroundSYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years.MethodsIn the study, we reported two male patients with familial SYN1 variants related neurodevelopmental disorders from Asian population. Previously published cases with significant SYN1 variants from the literature were also included to analyze the phenotype and genotype of the disorder.ResultsTwo maternally inherited SYN1 variants, including c.C1076A, p.T359K in proband A and c.C1444T, p. Q482X in proband B (NM_133499) were found, which have never been described in detail. Combining with our research, all reported probands were male in the condition, whose significant SYN1 variants were inherited from their asymptomatic or mild affected mother. Although the disorder encompasses three main clinical presentations: mental deficiency, easily controlled reflex seizure and behavior problems, patients’ clinical manifestations vary in genders and individuals, even in the same pedigree.ConclusionWe firstly reported two familial SYN1-related neurodevelopmental disorders in Asian pediatric patients. Gender and phenotype differences should be highly valued in the disorder.
Highlights
Synapsin I (SYN1) encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis
Variants in SYN1 gene are related with X-linked epilepsy with variable learning disabilities and behavior disorders (OMIM 300491) and X-linked intellectual disability (OMIM 300115) [4]
We speculated that defects in the middle motifs of Synapsin I, including domain B, C and D, are inclined to lead to neurodevelopmental disorders in human after birth, while the possible harmfulness of variants in the other domains remain unknown
Summary
SYN1 encodes synapsin I, which is a neuronal phosphoprotein involving in regulating axonogenesis and synaptogenesis. Variants in the gene have been associated with X-linked neurodevelopmental disorders in recent years. SYN1(OMIM 313440) encodes Synapsin I protein, forming synaptic vesicles (SV) with other Synapsin subtypes including Synapsin II and Synapsin III, which has been confirmed to play crucial roles in synaptogenesis, synaptic neurotransmission, axonogenesis, and neuronal development in central and peripheral nervous system [1]. Biallelic disruption of SYN1 gene in mice results in seizures, autism-related behavioral abnormalities [3]. Variants in SYN1 gene are related with X-linked epilepsy with variable learning disabilities and behavior disorders (OMIM 300491) and (or) X-linked intellectual disability (OMIM 300115) [4]. Like other X-linked neurodevelopmental disorders such as Turner-type X-linked syndromic mental retardation (OMIM 309590), the disease’s clinical characteristics differ in gender.
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