Related Experiment Video

Updated: Sep 24, 2025

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
06:41

In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila

Published on: August 20, 2019

13.8K

De novo variants in the PABP domain of PABPC1 lead to developmental delay

Meret Wegler1, Xiangbin Jia2, Marielle Alders3

  • 1Institute of Human Genetics, University Medical Center, Leipzig, Germany.

Genetics in Medicine : Official Journal of the American College of Medical Genetics
|May 5, 2022
PubMed

Insights

Genetic variants in PABPC1 are linked to developmental delay (DD) by impairing neural progenitor cell proliferation and neurogenesis. These findings highlight PABPC1

Area of Science:

  • Genetics
  • Neuroscience
  • Molecular Biology

Background:

  • Developmental delay (DD) is a complex condition with diverse etiologies.
  • Understanding the genetic underpinnings of DD is crucial for diagnosis and potential therapies.

Purpose of the Study:

  • To investigate the role of Poly(A)-binding protein 1 (PABPC1) in developmental delay.
  • To identify the functional impact of PABPC1 variants found in individuals with DD.

Main Methods:

  • Exome sequencing and bioinformatics analysis to identify PABPC1 variants.
  • In silico molecular modeling and coimmunoprecipitation to assess protein interactions.
  • In utero electroporation in mouse embryos to study PABPC1 function in neurogenesis.

Main Results:

  • Four probands presented with DD, expressive speech delay, autistic features, seizures, and behavioral disorders due to heterozygous de novo PABPC1 variants.
  • Variants clustered in the PABP domain, predicted to reduce binding affinity to RNA metabolism proteins like PAIP2.
  • Coimmunoprecipitation confirmed weakened PABPC1-PAIP2 interaction. PABPC1 knockdown in mouse embryos reduced neural progenitor cell proliferation, with most variants failing to rescue this effect.

Conclusions:

  • Pathogenic variants in the PABPC1 PABP domain contribute to DD.
  • These variants likely impair neurogenesis during cortical development by interfering with translation initiation.
Abstract

Keywords:
EpilepsyExomeIntellectual disabilityNeural progenitor cellsNeurodevelopmental disorder

More Related Videos

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

9.9K
A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations08:22

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

8.7K

Related Concept Videos

Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.1K
Genomic Imprinting and Inheritance02:30

Genomic Imprinting and Inheritance

Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
35.4K
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.
103.2K
Teratogenicity01:07

Teratogenicity

The ability of a drug to produce structural deformations and functional abnormalities in the developing embryo or the fetus is called teratogenicity, and the drug producing this effect is known as a teratogen. Teratogenic effects include stillbirth, miscarriage, intrauterine growth restriction, and neurocognitive delay. A teratogen may affect the embryo at different stages of development, which is important in determining the type and extent of the damage. During blastocyst formation, the early...
2.9K
Restarting Stalled Replication Forks02:37

Restarting Stalled Replication Forks

DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
5.9K