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Published on: April 1, 2019
TPH2 polymorphisms and expression in Prader-Willi syndrome subjects with differing genetic subtypes.
Rebecca S Henkhaus1, Douglas C Bittel, Merlin G Butler
1Departments of Psychiatry & Behavioral Sciences and Pediatrics, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS, 66160, USA.
Journal of Neurodevelopmental Disorders
|December 1, 2011
Summary
Prader-Willi syndrome (PWS) subtypes show altered TPH2 gene expression, impacting brain serotonin. Deletion subtypes exhibit lower TPH2 expression than UPD subtypes or controls.
Area of Science:
- Genetics
- Neuroscience
- Molecular Biology
Background:
- Prader-Willi syndrome (PWS) is a genetic imprinting disorder affecting chromosome 15q11-q13, causing developmental and behavioral issues.
- Serotonin dysregulation is implicated in PWS, influencing eating and compulsive behaviors.
- Genetic subtypes of PWS, including deletion and maternal uniparental disomy (UPD), present distinct clinical features.
Purpose of the Study:
- Investigate the tryptophan hydroxylase gene (TPH2), crucial for brain serotonin synthesis, in PWS.
- Analyze TPH2 gene polymorphisms, transcript expression, and their correlation with PWS genetic subtypes.
- Determine if TPH2 expression differences contribute to the distinct PWS phenotypes.
Main Methods:
- Collected DNA and RNA from lymphoblastoid cell lines of 12 PWS patients and 12 controls.
- Determined PWS genetic subtypes (deletion vs. UPD).
- Analyzed TPH2 gene polymorphisms and quantified TPH2 transcript expression using quantitative RT-PCR.
Main Results:
- TPH2 polymorphism frequencies were similar between PWS and control groups.
- PWS deletion subjects showed increased TPH2 expression with certain polymorphisms.
- Both PWS deletion and UPD subtypes had significantly lower TPH2 expression than controls.
- PWS deletion subjects had significantly lower TPH2 expression compared to PWS UPD subjects.
Conclusions:
- TPH2 expression is significantly reduced in PWS, particularly in the deletion subtype.
- Genetic subtype influences TPH2 expression levels in Prader-Willi syndrome.
- Further research is needed to understand the mechanisms behind reduced TPH2 expression in PWS deletion, including gene interactions.
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