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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
Biallelic Variants in SLC27A3 Cause a Complex Form of Neurodegeneration with Brain Iron Accumulation
Lorena Travaglini1, Cherim Jeon2, Teresa Rizza1
1Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Background:
Complex lipid metabolism is one of the main biological pathways disrupted in neurodegeneration with brain iron accumulation (NBIA). SLC27A3 gene encodes for the very long-chain acyl-CoA synthetase 3, an acyl-CoA ligase that activates long and very long-chain fatty acids.
Objective:
We report on a 19-year-old patient with an NBIA pattern harboring a homozygous, nonsense SLC27A3 variant.
Methods:
SLC27A3 variants were identified using whole exome sequencing (WES). Their impact on protein function was assessed in patient fibroblasts using Western blot analysis, aerobic metabolism analysis, and fatty acid trafficking assays.
Results:
The patient presented with progressive ataxia, neuropathy, optic atrophy, cognitive deterioration, mood disorder, and brain iron accumulation. WES unraveled the homozygous c.1138C>T, p.(Arg380Ter) variant in the SLC27A3 gene. Functional studies showed that proband's variants eliminate protein expression, severely impair mitochondrial respiration, and disrupt lipid turnover.
Conclusion:
Our results suggest that SLC27A3 biallelic nonsense variant may represent a novel cause of NBIA. © 2025 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Translation
Translation is the process of synthesizing proteins from the genetic information carried by messenger RNA (mRNA). Following transcription, it constitutes the final step in the expression of genes. This process is carried out by ribosomes, complexes of protein and specialized RNA molecules. Ribosomes, transfer RNA (tRNA), and other proteins produce a chain of amino acids—the polypeptide—as the end product of translation.
Translation Produces the Building Blocks of...
Translation
Translation Produces the Building Blocks of Life
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