Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome
ABSTRACT 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...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Annals of Clinical and Translational Neurology |
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| Online Access: | https://doi.org/10.1002/acn3.70065 |
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| _version_ | 1849404883951681536 |
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| author | Maria Gabriela Otero Christina Freeman Ruchi Shah Renkui Bai Hong Cui Marian Castro Zachary Myers Eric Choy Derek Chan Molly Easter Sophia Y. Zhao Madeline Babros Ruchi Garg Matthew Deardorff Franklin Moser Tyler Mark Pierson |
| author_facet | Maria Gabriela Otero Christina Freeman Ruchi Shah Renkui Bai Hong Cui Marian Castro Zachary Myers Eric Choy Derek Chan Molly Easter Sophia Y. Zhao Madeline Babros Ruchi Garg Matthew Deardorff Franklin Moser Tyler Mark Pierson |
| author_sort | Maria Gabriela Otero |
| collection | DOAJ |
| description | ABSTRACT 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. |
| format | Article |
| id | doaj-art-e0410a8f12104a0090e2d00e63576e41 |
| institution | Kabale University |
| issn | 2328-9503 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj-art-e0410a8f12104a0090e2d00e63576e412025-08-20T03:36:49ZengWileyAnnals of Clinical and Translational Neurology2328-95032025-08-011281693169710.1002/acn3.70065Compound Heterozygous MRPS14 Variants Associated With Leigh SyndromeMaria Gabriela Otero0Christina Freeman1Ruchi Shah2Renkui Bai3Hong Cui4Marian Castro5Zachary Myers6Eric Choy7Derek Chan8Molly Easter9Sophia Y. Zhao10Madeline Babros11Ruchi Garg12Matthew Deardorff13Franklin Moser14Tyler Mark Pierson15Board of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABiomedical Sciences Cedars‐Sinai Medical Center Los Angeles California USAGeneDx Gaithersburg Maryland USAGeneDx Gaithersburg Maryland USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USAPediatric Congenital Heart Program at Cedars‐Sinai Guerin Children's and Smidt Heart Institute Cedars‐Sinai Medical Center Los Angeles California USADepartment of Pathology and Laboratory Medicine Children's Hospital Los Angeles California Los Angeles USADivision of Clinical Neuroradiology and Interventional Neuroradiology Cedars‐Sinai Medical Center Los Angeles California USABoard of Governors Regenerative Medicine Institute Cedars‐Sinai Medical Center Los Angeles California USAABSTRACT 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.https://doi.org/10.1002/acn3.70065Leigh Syndromemitochondrial ribosomeMRPS14oxidative phosphorylation |
| spellingShingle | Maria Gabriela Otero Christina Freeman Ruchi Shah Renkui Bai Hong Cui Marian Castro Zachary Myers Eric Choy Derek Chan Molly Easter Sophia Y. Zhao Madeline Babros Ruchi Garg Matthew Deardorff Franklin Moser Tyler Mark Pierson Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome Annals of Clinical and Translational Neurology Leigh Syndrome mitochondrial ribosome MRPS14 oxidative phosphorylation |
| title | Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome |
| title_full | Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome |
| title_fullStr | Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome |
| title_full_unstemmed | Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome |
| title_short | Compound Heterozygous MRPS14 Variants Associated With Leigh Syndrome |
| title_sort | compound heterozygous mrps14 variants associated with leigh syndrome |
| topic | Leigh Syndrome mitochondrial ribosome MRPS14 oxidative phosphorylation |
| url | https://doi.org/10.1002/acn3.70065 |
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