Related Experiment Video
Updated: Jun 4, 2025
00:06
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
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EEFSEC deficiency: A selenopathy with early-onset neurodegeneration
Lucia Laugwitz1, Rebecca Buchert2, Patricio Olguín3
1Institute of Medical Genetics and Applied Genomics, University of Tübingen, 72076 Tübingen, Germany; Neuropediatrics, General Paediatrics, Diabetology, Endocrinology and Social Paediatrics, University of Tübingen, University Hospital Tübingen, 72016 Tübingen, Germany.
American Journal of Human Genetics
|January 3, 2025
Summary
Genetic variants in EEFSEC cause a rare neurodegenerative disorder due to selenoprotein deficiency. This inborn error of selenocysteine metabolism leads to progressive neurological symptoms and cerebellar pathology.
Area of Science:
- Genetics
- Neuroscience
- Biochemistry
Background:
- Inborn errors in selenoprotein expression are linked to neurodegeneration.
- Selenoproteins and their biosynthetic factors are crucial for cellular function.
Purpose of the Study:
- To investigate the role of eukaryotic elongation factor selenocysteine 1 (EEFSEC) variants in neurodegenerative disorders.
- To elucidate the molecular mechanisms underlying EEFSEC deficiency.
Main Methods:
- Exome and genome sequencing to identify EEFSEC variants in affected individuals.
- In vitro functional assays to assess EEFSEC variant activity.
- Development of a Drosophila model to study disease pathology.
Main Results:
- Identified six distinct bi-allelic EEFSEC variants in nine individuals from eight families.
- EEFSEC variants impaired protein function, leading to reduced selenoprotein levels.
- A Drosophila model exhibited motor deficits and synaptic defects mirroring human phenotypes.
Conclusions:
- EEFSEC deficiency is an autosomal recessive disorder causing progressive neurodegeneration.
- This study establishes a link between selenocysteine metabolism defects and neurodegeneration.
- Findings suggest potential therapeutic strategies targeting selenoprotein pathways.
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