Related Experiment Video
Updated: Jun 24, 2026
06:41
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
The common BDNF polymorphism may be a modifier of disease severity in Rett syndrome
B Ben Zeev1, A Bebbington, G Ho
1Pediatric Neurology Unit, Safra Pediatric Hospital, Sheba Medical Center, Ramat-Gan, Israel.
Neurology
|April 8, 2009
Summary
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism may modify Rett syndrome (RTT) severity. This common BDNF variant influences disease progression and seizure risk in RTT patients with specific MECP2 mutations.
Area of Science:
- Neuroscience
- Genetics
- Developmental Biology
Background:
- Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl CpG-binding protein 2 (MECP2) gene.
- Brain-derived neurotrophic factor (BDNF) is crucial for neuronal survival and plasticity, with its expression regulated by MeCP2.
- A common BDNF polymorphism (Val66Met) is associated with various neuropsychiatric disorders.
Purpose of the Study:
- To investigate the association between the BDNF Val66Met polymorphism and Rett syndrome severity.
- To determine if the BDNF polymorphism modifies disease course in RTT patients.
Main Methods:
- Examined 125 mutation-positive RTT patients from Australian and Israeli cohorts.
- Assessed disease severity using the modified Percy score.
- Utilized regression methods to analyze the association between BDNF polymorphism and RTT severity.
Main Results:
- Heterozygosity for the BDNF Val66Met polymorphism was linked to slightly increased RTT severity (2.1 points).
- In patients with the MECP2 p.R168X mutation, BDNF Val66Met heterozygosity correlated with a 6-point increase in severity score.
- Individuals with p.R168X and BDNF Val66Met heterozygosity had a significantly higher risk of seizure onset (HR 5.3).
Conclusions:
- The BDNF Val66Met polymorphism acts as a genetic modifier of Rett syndrome severity, alongside MECP2 mutation type and X-chromosome skewing.
- BDNF's role in pathogenesis suggests potential therapeutic targets for RTT.
Related Concept Videos
01:11Genetic Lingo
Overview
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:49Multiple Allele Traits
The Concept of Multiple Allelism
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:43Incomplete Dominance
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.