Paternally Inherited GABRB3 Intragenic Deletion in a Boy with Autistic Features and Angelman Syndrome Phenotype–Case Report and Literature Review

Krzysztof SzczaaUba,Ilona Jaszczuk

doi:10.4172/2165-7890.1000182

Abstract

We report on a 4 year old patient with a unique paternally inherited single-exon GABRB3 gene deletion and clinical findings of severe speech delay, intellectual disability, autistic features, unusual behavior, tremor, and history of seizures and gait abnormalities. Similarities and significant differences with other cases involving rearrangements of 15q11-q13 are discussed. Further on, we provide literature review of the clinical picture of GABRB3 mutations.

Highlights

Recurrent rearrangements in particular chromosomal regions have been deemed causative for number of neurodevelopmental disorders
We hypothesize that in our patients the deletion leads to the phenotype of intellectual disability, behavioural abnormalities, autistic features, and seizures that are consistent with Angelman syndrome phenotype
Gamma-aminobutyric acid (GABA) receptors are a family of proteins involved in the GABAergic neurotransmission of the mammalian central nervous system

Summary

Introduction

Recurrent rearrangements in particular chromosomal regions have been deemed causative for number of neurodevelopmental disorders. Microdeletions or microduplications (or so called copy number variants-CNVs) in 15q11-q13 region lead to a variety of phenotypes, including Angelman (AS) and Prader-Willi (PWS) syndromes as well as autism spectrum disorders [1]. Of the number of genes residing in the imprinted region, GABRB3 encodes one of the subunits of GABA A receptor [4]. The proper function and/or the number of GABA receptors may be affected by the mutations of GABRB3 gene (Figure 1). Single nucleotide variants (SNVs) in GABRB3 account for childhood absence epilepsy and, just recently, have been observed in cases of encephalopathy with intractable seizures or non-syndromic intellectual disability [5,6]. We hypothesize that in our patients the deletion leads to the phenotype of intellectual disability, behavioural abnormalities, autistic features, and seizures that are consistent with Angelman syndrome phenotype. We discuss the available literature on GABRB3 function and the role of pathogenic variants within this gene

Case Report

Discussion

Regulatory mutations Gross deletions Gross insertions Small insertions Splicing