{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:04Z","timestamp":1753892104720,"version":"3.41.2"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T00:00:00Z","timestamp":1714003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>There are few reports of infantile mitochondrial DNA depletion syndrome (MDDS) caused by variants in <jats:italic>RRM2B<\/jats:italic> and the correlation between genotype and phenotype has rarely been analyzed in detail. This study investigated an infantile patient with MDDS, from clinical characteristics to genetic causes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Routine physical examinations, laboratory assays, which included gas chromatography\u2013mass spectrometry of blood and urine, and MRI scans were performed to obtain an exact diagnosis. Whole-exome sequencing was used to pinpoint the abnormal gene and bioinformatic analyses were performed on the identified variant.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The case presented with progressive neurologic deterioration, failure to thrive, respiratory distress and lactic acidosis. Sequencing revealed that the patient had a homozygous novel missense variant, c.155T&amp;gt;C (p.Ile52Thr), in exon 2 of the <jats:italic>RRM2B<\/jats:italic> gene. Multiple lines of bioinformatic evidence suggested that this was a likely detrimental variant. In addition, reported <jats:italic>RRM2B<\/jats:italic> variants were compiled from the relevant literature to analyze disease etiology. We found a distinctive distribution of genotypes across disease manifestations of different severity. Pathogenic alleles of <jats:italic>RRM2B<\/jats:italic> were significantly enriched in MDDS cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The novel variant is a likely genetic cause of MDDS. It expands our understanding of the pathogenic variant spectrum and the contribution of the <jats:italic>RRM2B<\/jats:italic> gene to the disease spectrum of MDDS.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2024.1363728","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T04:33:26Z","timestamp":1714019606000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: A novel RRM2B variant in a Chinese infant with mitochondrial DNA depletion syndrome and collective analyses of RRM2B variants for disease 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