UBE3A and Its Link With Autism.

Naman Vatsa,Nihar Ranjan Jana

doi:10.3389/fnmol.2018.00448

Abstract

UBE3A is a dual function protein consisting of ubiquitin ligase as well as transcriptional co-activator function. UBE3A gene is imprinted in the brain with preferential maternal-specific expression particularly in the neuron and loss of activity of the maternally inherited UBE3A causes Angelman syndrome (AS), characterized by severe mental retardation, lack of speech, seizures and autistic features. Interestingly, duplication, triplication, or gain-of-function mutations in the UBE3A gene are also linked with autism clinically distinguished by social impairments and stereotyped behaviors. These findings indicate that the expression and activity of UBE3A must be tightly regulated during brain development and UBE3A might be playing a crucial role in controlling synaptic function and plasticity through proteasome-mediated degradation as well as transcriptional regulation of its target proteins. In fact, several recent reports demonstrated the role of UBE3A in the modulation of synaptic function and plasticity. This review focuses on the critical role of UBE3A in regulating the synaptic function and how its altered activity is associated with autism.

Highlights

International classification of diseases (ICD-10) describes autism as an early onset neurodevelopmental disorder with three major characteristics feature: lack of communication, lack of social skills, and repetitive stereotyped behavior
With the extensive study in multiple new cases, the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) updated this definition in 2013, wherein, delayed language development was removed from the list of criteria and autism covered a host of diseases redefining itself as an autism spectrum disorder (ASD)
The loss of function of maternally inherited UBE3A is associated with Angelman syndrome (AS), a neurodevelopmental disorder with severe mental retardation along with autistic features (Malzac et al, 1998; Moncla et al, 1999), making UBE3A a potential candidate gene to be studied for better understanding of autism

Summary

Introduction

International classification of diseases (ICD-10) describes autism as an early onset neurodevelopmental disorder with three major characteristics feature: lack of communication, lack of social skills, and repetitive stereotyped behavior. The loss of function of maternally inherited UBE3A is associated with Angelman syndrome (AS), a neurodevelopmental disorder with severe mental retardation along with autistic features (Malzac et al, 1998; Moncla et al, 1999), making UBE3A a potential candidate gene to be studied for better understanding of autism.

Results

Conclusion