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Updated: May 9, 2025
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Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
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Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome
Maria Gabriela Otero1, Christina Freeman1, Ruchi Shah2,3
1Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Annals of Clinical and Translational Neurology
|May 3, 2025
Summary
We identified new mutations in the MRPS14 gene, causing a rare mitochondrial disorder (COXPD38) with Leigh Syndrome. This expands the known genetic causes of this severe neurological condition.
Area of Science:
- Genetics
- Mitochondrial Biology
- Neurology
Background:
- MRPS14 (uS14m) is crucial for mitochondrial protein synthesis.
- MRPS14-related disorder (COXPD38) is extremely rare, with only one prior case reported.
- Mitochondrial disorders often present with complex multi-systemic symptoms.
Purpose of the Study:
- To report a novel case of MRPS14-related disorder.
- To characterize the clinical and molecular findings in a new patient.
- To expand the understanding of genetic causes for Leigh Syndrome.
Main Methods:
- Genetic sequencing to identify MRPS14 variants.
- Clinical evaluation including neuroimaging (MRI) and spectroscopy.
- Biochemical analysis using fibroblast Western blots for protein levels.
Main Results:
- A patient presented with motor/language delays and elevated lactate/alanine.
- Brain MRI confirmed findings consistent with Leigh Syndrome.
- Novel compound heterozygous MRPS14 variants (p.Asp37Asn, p.Asn60Asp) were identified.
- Decreased MRPS14 and COX2 protein levels were observed in patient fibroblasts.
Conclusions:
- The identified MRPS14 variants are pathogenic.
- This case expands the clinical spectrum and genetic basis of MRPS14-related disorders.
- Further research into MRPS14 function and therapeutic strategies is warranted.
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