A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype

IF 1.8 4区医学 Q3 GENETICS & HEREDITY

Molecular Genetics and Metabolism Reports Pub Date : 2025-02-06 DOI:10.1016/j.ymgmr.2025.101198

Hiroyuki Iijima , Yuko Tsujioka , Yoshiyuki Tsutsumi , Gen Nishimura , Yasushi Okazaki , Kei Murayama , Mitsuru Kubota , Akira Ohtake

{"title":"A girl with intragenic variants in MARS2 and a chondrodysplasia phenotype","authors":"Hiroyuki Iijima , Yuko Tsujioka , Yoshiyuki Tsutsumi , Gen Nishimura , Yasushi Okazaki , Kei Murayama , Mitsuru Kubota , Akira Ohtake","doi":"10.1016/j.ymgmr.2025.101198","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>The human mitochondrial methionyl-tRNA is crucial for mitochondrial translation, serving as both initiator and elongator in polypeptide chains. The <em>MARS2</em> gene is responsible for binding methionine to mitochondrial tRNA. The clinical characteristics of <em>MARS2</em> 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.</div></div><div><h3>Case presentation</h3><div>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 <em>MARS2</em> 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.</div></div><div><h3>Conclusion</h3><div>The skeletal phenotype may be a syndromic component of this disorder associated with <em>MARS2</em> intragenic variants.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"42 ","pages":"Article 101198"},"PeriodicalIF":1.8000,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Genetics and Metabolism Reports","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2214426925000138","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

背景人类线粒体蛋氨酰-tRNA 对线粒体翻译至关重要，它既是多肽链的启动子，也是多肽链的延伸子。MARS2 基因负责将蛋氨酸与线粒体 tRNA 结合。MARS2 基因内变异体的临床特征在很大程度上仍不为人所知，因为只有一对同胞的报道。本例患者表现为精神运动发育迟缓、生长发育障碍和脊柱发育不良，在婴儿期就引起了关注，并随着年龄的增长而恶化。病例介绍一名 7 个月大的日本女孩因发育不良、喂养困难和精神运动发育迟缓而就诊。放射学检查显示全身骨骼改变，包括轻度脊柱发育不良和髂骨异常，类似粘多糖病；但尿液中的糖胺聚糖水平和滤纸血液中的α-L-尿糖苷酶活性正常。33 个月大时，她出现了高泌乳素血症，遗传分析显示，她的 MARS2 基因存在复合杂合子新变异（NM_138395.4：c. [277G > A]；[409C > T]：p. （[Asp93Asn]；[Arg137Cys]）。开始补充维生素后，她的生长发育有所改善。2 岁和 4 岁时的放射学检查显示了她的骨骼表型：椎体前凸的板状软骨症；股骨近端骨骺过大；轻度腕骨发育不良。使用皮肤成纤维细胞进行的线粒体呼吸链活性检查结果显示在正常范围内。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Genetics and Metabolism Reports Biochemistry, Genetics and Molecular Biology-Endocrinology

CiteScore

4.00

自引率

5.30%

发文量

105

审稿时长

33 days

期刊介绍： Molecular Genetics and Metabolism Reports is an open access journal that publishes molecular and metabolic reports describing investigations that use the tools of biochemistry and molecular biology for studies of normal and diseased states. In addition to original research articles, sequence reports, brief communication reports and letters to the editor are considered.