{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T10:36:24Z","timestamp":1785753384422,"version":"3.56.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ital J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Pyruvate dehydrogenase (PDH) deficiency is an uncommon condition responsible for primary refractory lactic acidosis, and PDH E1\u03b2 (\n                      <jats:italic>PDHB<\/jats:italic>\n                      ) subunit gene mutation rarely causes of PDH deficiency. We described a missense mutation of\n                      <jats:italic>PDHB<\/jats:italic>\n                      gene in a neonate with PDH deficiency, and verified the mutation damages PDH activity in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Whole exome sequencing (WES) was used to discover the missense mutation. We constructed the recombinant eukaryotic recombinant expression vector, the phage-PDHB-wt\/mut, containing human full-length wild-type (NM_000925.4) or mutant (c.575G\u2009&gt;\u2009T)\n                      <jats:italic>PDHB<\/jats:italic>\n                      gene, and transfected vector into 293T cells. Western blot was performed to assess PDH protein stability, PDH activity was measured.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A 37-week-gestation male infant was noted to have refractory lactic acidosis, growth retardation, and neurodevelopmental anomalies with abnormal brain magnetic resonance (MR) findings, starting with convulsive seizures at 3\u00a0months of age. WES analysis revealed the homozygous missense mutations in the\n                      <jats:italic>PDHB<\/jats:italic>\n                      gene, which was c.575G\u2009&gt;\u2009T (p.Arg192Leu) in exon 6. This missense mutation of\n                      <jats:italic>PDHB<\/jats:italic>\n                      was predicted to be harmful by bioinformatics software including Sorting Intolerant From Tolerant (SIFT), Polyphen2, LRT, and Mutation Taster. Western blot showed that normal PDH protein expression was significantly decreased in the phage -PDHB-mut transfected cells than that in the phage -PDHB-wt transfected cells (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). PDH activities analysis revealed that PDH activity was significantly decreased in the phage -PDHB-mut transfected cells than that in the phage -PDHB-wt transfected cells (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      c.575G\u2009&gt;\u2009T (p.Arg192Leu) in\n                      <jats:italic>PDHB<\/jats:italic>\n                      gene is a pathogenic missense mutation, which causes PDH deficiency in autosomal recessive inheritance mode.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13052-025-01917-9","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T04:57:10Z","timestamp":1741237030000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A missense mutation in PDHB gene: identification of the patient with pyruvate dehydrogenase deficiency and demonstration of pathogenicity in vitro"],"prefix":"10.1186","volume":"51","author":[{"given":"Ying","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Yi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6785-0511","authenticated-orcid":false,"given":"Tao","family":"Bo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"issue":"1","key":"1917_CR1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.ymgme.2011.09.032","volume":"105","author":"KP Patel","year":"2012","unstructured":"Patel KP, O\u2019Brien TW, Subramony SH, Shuster J, Stacpoole PW. 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We confirm that we had obtained a written informed consent from the patient\u2019s parent because the participant is under 16\u00a0years old.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"We had written and signed consent to publish the information from the patients or their guardians prior to submission. Written informed consent was obtained from the patient for publication of this case report and accompanying images.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"66"}}