The neurodevelopmental spectrum of synaptic vesicle cycling disorders.

Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1471-4159 (Electronic) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE

Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
Original Publication: New York : Raven Press

Epilepsy/*metabolism ; Intellectual Disability/*metabolism ; Movement Disorders/*metabolism ; Neurodevelopmental Disorders/*metabolism ; Synaptic Vesicles/*metabolism; Animals ; Humans ; Mutation/genetics ; Neurodevelopmental Disorders/genetics

In this review, we describe and discuss neurodevelopmental phenotypes arising from rare, high penetrance genomic variants which directly influence synaptic vesicle cycling (SVC disorders). Pathogenic variants in each SVC disorder gene lead to disturbance of at least one SVC subprocess, namely vesicle trafficking (e.g. KIF1A and GDI1), clustering (e.g. TRIO, NRXN1 and SYN1), docking and priming (e.g. STXBP1), fusion (e.g. SYT1 and PRRT2) or re-uptake (e.g. DNM1, AP1S2 and TBC1D24). We observe that SVC disorders share a common set of neurological symptoms (movement disorders, epilepsies), cognitive impairments (developmental delay, intellectual disabilities, cerebral visual impairment) and mental health difficulties (autism, ADHD, psychiatric symptoms). On the other hand, there is notable phenotypic variation between and within disorders, which may reflect selective disruption to SVC subprocesses, spatiotemporal and cell-specific gene expression profiles, mutation-specific effects, or modifying factors. Understanding the common cellular and systems mechanisms underlying neurodevelopmental phenotypes in SVC disorders, and the factors responsible for variation in clinical presentations and outcomes, may translate to personalized clinical management and improved quality of life for patients and families.
(© 2020 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

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MC_UU_00005/16 United Kingdom MRC_ Medical Research Council; G101400 United Kingdom MRC_ Medical Research Council; United Kingdom WT_ Wellcome Trust

Keywords: Synaptic vesicle cycle; cerebral visual impairment; epilepsy; intellectual disability; mental health; movement disorders

Date Created: 20200802 Date Completed: 20210617 Latest Revision: 20210617

20240829

10.1111/jnc.15135

32738165