Compound Heterozygous <i>MRPS14</i> Variants Associated With Leigh Syndrome
MRPS14 (uS14m) is a nuclear-encoded ribosomal protein important for mitochondria-specific translation. To date, only a single individual with a recessive MRPS14-related disorder (also known as COXPD38) has been reported. We report an additional subject possessing novel compound heterozygous MRPS14 variants (p.Asp37Asn, p.Asn60Asp). The subject presented at 2 years with motor and language delays associated with elevated serum lactate/alanine levels. Brain MRI showed a constellation of signal abnormalities consistent with Leigh Syndrome, while MR spectroscopy had an increased lactate peak. Western blots of fibroblasts showed decreased MRPS14 and COX2 protein levels. These results support the pathogenicity of the MRPS14 variants identified here.
Authors
- Franklin G. Moser (ORCID: https://orcid.org/0000-0001-5267-2667)
- Molly Easter (ORCID: https://orcid.org/0000-0001-8208-7266)
- Ruchi Shah (ORCID: https://orcid.org/0000-0002-9533-1747)
- Marián Castro (ORCID: https://orcid.org/0000-0002-4732-1966)
- María Gabriela Otero (ORCID: https://orcid.org/0000-0001-6263-2466)
- Zachary Myers (ORCID: https://orcid.org/0000-0002-7225-0290)
- Tyler Mark Pierson (ORCID: https://orcid.org/0000-0003-1985-3671)
- Renkui Bai
- Derek Y. C. Chan (ORCID: https://orcid.org/0000-0002-2156-074X)
- Ernest Choy (ORCID: https://orcid.org/0000-0003-4459-8609)
- Madeline Babros
- Hong Cui (ORCID: https://orcid.org/0000-0003-0537-5533)
- Matthew A. Deardorff
- Ruchi Garg
- Christina Freeman
- S. Zhao
Institutions
- Cedars-Sinai Medical Center (US)
- Children's Hospital of Los Angeles (US)
- Cedars-Sinai Smidt Heart Institute (US)
Publication Details
- Journal
- Annals of Clinical and Translational Neurology
- Published
- 2025-05-02
- DOI
- https://doi.org/10.1002/acn3.70065
- Citations
- 2
- Primary Topic
- Mitochondrial Function and Pathology
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Cedars-Sinai Medical Center