A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype
Background: The human mitochondrial methionyl-tRNA is crucial for mitochondrial translation, serving as both initiator and elongator in polypeptide chains. The MARS2 gene is responsible for binding methionine to mitochondrial tRNA. The clinical characteristics of MARS2 intragenic variants are still...
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Elsevier
2025-03-01
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| Series: | Molecular Genetics and Metabolism Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2214426925000138 |
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| author | Hiroyuki Iijima Yuko Tsujioka Yoshiyuki Tsutsumi Gen Nishimura Yasushi Okazaki Kei Murayama Mitsuru Kubota Akira Ohtake |
| author_facet | Hiroyuki Iijima Yuko Tsujioka Yoshiyuki Tsutsumi Gen Nishimura Yasushi Okazaki Kei Murayama Mitsuru Kubota Akira Ohtake |
| author_sort | Hiroyuki Iijima |
| collection | DOAJ |
| description | Background: The human mitochondrial methionyl-tRNA is crucial for mitochondrial translation, serving as both initiator and elongator in polypeptide chains. The MARS2 gene is responsible for binding methionine to mitochondrial tRNA. The clinical characteristics of MARS2 intragenic variants are still largely unknown, since only a pair of siblings has been reported. The present patient presented with psychomotor developmental delay, growth failure, and spondylar dysplasia, which attracted attention in infancy and deteriorated with age. Case presentation: A 7-month-old Japanese girl presented with failure to thrive, feeding difficulties, and psychomotor developmental delay. Radiological examination showed generalized skeletal alterations including mild spondylar dysplasia and abnormal ilia, which resembled mucopolysaccharidosis; however, the urinary glycosaminoglycan levels and alpha-L-iduronidase activity in the filter paper blood were normal. At age 33 months, she showed hyperlactatemia, and genetic analysis showed compound heterozygous novel variants (NM_138395.4: c.[277G > A]; [409C > T]: p.([Asp93Asn]; [Arg137Cys])) in the MARS2 gene. After starting vitamin supplementation, her growth and development improved. Radiological examination at ages 2 and 4 years demonstrated a skeletal phenotype: platyspondyly with anterior beaking of the vertebral bodies; large proximal femoral epiphyses; and mild brachymesophalangy. The results of the mitochondrial respiratory chain activity examination using skin fibroblasts were within the normal range. Conclusion: The skeletal phenotype may be a syndromic component of this disorder associated with MARS2 intragenic variants. |
| format | Article |
| id | doaj-art-0a137b087c1d4865a55286ab05389876 |
| institution | Kabale University |
| issn | 2214-4269 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Genetics and Metabolism Reports |
| spelling | doaj-art-0a137b087c1d4865a55286ab053898762025-02-07T04:47:33ZengElsevierMolecular Genetics and Metabolism Reports2214-42692025-03-0142101198A girl with intragenic variants in MARS2 and a chondrodysplasia phenotypeHiroyuki Iijima0Yuko Tsujioka1Yoshiyuki Tsutsumi2Gen Nishimura3Yasushi Okazaki4Kei Murayama5Mitsuru Kubota6Akira Ohtake7Department of Clinical Genomics & Pediatrics, Faculty of Medicine, Saitama Medical University, Moroyama, Saitama, Japan; Department of General Pediatrics & Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo, Japan; Corresponding author at: Department of General Pediatrics & Interdisciplinary Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan.Department of Radiology, Keio University School of Medicine, Tokyo, JapanDepartment of Radiology, National Center for Child Health and Development, Tokyo, JapanCenter for Intractable Diseases, Saitama Medical University Hospital, Saitama, JapanDiagnostics and Therapeutic of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, JapanDiagnostics and Therapeutic of Intractable Diseases, Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, JapanDepartment of General Pediatrics & Interdisciplinary Medicine, National Center for Child Health and Development, Tokyo, JapanDepartment of Clinical Genomics & Pediatrics, Faculty of Medicine, Saitama Medical University, Moroyama, Saitama, JapanBackground: The human mitochondrial methionyl-tRNA is crucial for mitochondrial translation, serving as both initiator and elongator in polypeptide chains. The MARS2 gene is responsible for binding methionine to mitochondrial tRNA. The clinical characteristics of MARS2 intragenic variants are still largely unknown, since only a pair of siblings has been reported. The present patient presented with psychomotor developmental delay, growth failure, and spondylar dysplasia, which attracted attention in infancy and deteriorated with age. Case presentation: A 7-month-old Japanese girl presented with failure to thrive, feeding difficulties, and psychomotor developmental delay. Radiological examination showed generalized skeletal alterations including mild spondylar dysplasia and abnormal ilia, which resembled mucopolysaccharidosis; however, the urinary glycosaminoglycan levels and alpha-L-iduronidase activity in the filter paper blood were normal. At age 33 months, she showed hyperlactatemia, and genetic analysis showed compound heterozygous novel variants (NM_138395.4: c.[277G > A]; [409C > T]: p.([Asp93Asn]; [Arg137Cys])) in the MARS2 gene. After starting vitamin supplementation, her growth and development improved. Radiological examination at ages 2 and 4 years demonstrated a skeletal phenotype: platyspondyly with anterior beaking of the vertebral bodies; large proximal femoral epiphyses; and mild brachymesophalangy. The results of the mitochondrial respiratory chain activity examination using skin fibroblasts were within the normal range. Conclusion: The skeletal phenotype may be a syndromic component of this disorder associated with MARS2 intragenic variants.http://www.sciencedirect.com/science/article/pii/S2214426925000138Amino-acyl tRNA synthetaseMARS2MitochondriaSpondylar dysplasia |
| spellingShingle | Hiroyuki Iijima Yuko Tsujioka Yoshiyuki Tsutsumi Gen Nishimura Yasushi Okazaki Kei Murayama Mitsuru Kubota Akira Ohtake A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype Molecular Genetics and Metabolism Reports Amino-acyl tRNA synthetase MARS2 Mitochondria Spondylar dysplasia |
| title | A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype |
| title_full | A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype |
| title_fullStr | A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype |
| title_full_unstemmed | A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype |
| title_short | A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype |
| title_sort | girl with intragenic variants in mars2 and a chondrodysplasia phenotype |
| topic | Amino-acyl tRNA synthetase MARS2 Mitochondria Spondylar dysplasia |
| url | http://www.sciencedirect.com/science/article/pii/S2214426925000138 |
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