Related Experiment Video

Updated: Feb 23, 2026

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
08:22

A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations

Published on: December 1, 2017

9.2K

Rapid whole-genome sequencing identifies a novel GABRA1 variant associated with West syndrome

Lauge Farnaes1, Shareef A Nahas1, Shimul Chowdhury1

  • 1Rady Children's Institute of Genomic Medicine (RCIGM), San Diego, California 92123, USA.

Cold Spring Harbor Molecular Case Studies
|September 3, 2017
PubMed

Insights

A novel genetic variant in the GABRA1 gene was identified in an infant with West syndrome. This finding links GABRA1 mutations to a specific form of this rare epilepsy disorder.

Area of Science:

  • Neurogenetics
  • Epileptology
  • Developmental Pediatrics

Background:

  • West syndrome is a severe infant epilepsy characterized by infantile spasms, hypsarrhythmia, and developmental delay.
  • Genetic factors play a crucial role in the etiology of West syndrome, but causative genes remain unidentified in many cases.

Observation:

  • A 9-month-old infant presented with infantile spasms, developmental delay, and esotropia, diagnosed with West syndrome.
  • Standard neuroimaging (MRI) was normal, but EEG showed hypsarrhythmia.
  • The infant showed improvement with topiramate and steroid treatment.

Findings:

  • Whole-genome sequencing identified a novel, de novo variant (c.789G>A, p.Met263Ile) in the GABRA1 gene, which encodes the alpha-1 subunit of the GABA-A receptor.
  • GABRA1 mutations are known to cause early infantile epileptic encephalopathy type 19 (EIEE19).

Implications:

  • This study suggests that the identified GABRA1 variant (p.Met263Ile) is associated with a distinct phenotype of West syndrome.
  • Understanding the genetic basis of West syndrome, particularly novel variants like this GABRA1 mutation, is crucial for accurate diagnosis and potential targeted therapies.

Keywords:
developmental regressiongeneralized neonatal hypotoniainfantile spasms

More Related Videos

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons08:04

Identification and Classification of Position-specific GABAA Receptor Subunit Missense Variants for Their Role In Hippocampal Pyramidal Neurons

Published on: June 6, 2025

1.6K
Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information09:37

Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information

Published on: August 15, 2019

10.5K

Related Concept Videos

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
15.9K
Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...
5.8K
Pleiotropy01:33

Pleiotropy

Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
43.6K
Sex-linked Disorders01:43

Sex-linked Disorders

Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
109.6K
Next-generation Sequencing03:00

Next-generation Sequencing

The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
99.3K
Single Nucleotide Polymorphisms-SNPs01:05

Single Nucleotide Polymorphisms-SNPs

A single nucleotide polymorphism or SNP is a single nucleotide variation at a specific genomic position in a large population. It is the most prevalent type of sequence variation found in the human genome. Point mutations that occur in more than 1% of the population qualify as SNPs. These are present once every 1000 nucleotides on an average in the human genome. Replacement of a purine with another purine (A/G) or a pyrimidine with another pyrimidine (C/T) is known as a transition. In contrast,...
18.7K