{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T14:25:55Z","timestamp":1787667955212,"version":"build-2736575974"},"reference-count":40,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Phenotypic variability in PTEN hamartoma tumor syndrome (PHTS) remains incompletely understood, and the contribution of additional rare genetic variants has rarely been functionally investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>\n                      We report a 9-year-old girl with macrocephaly, gastrointestinal manifestations, hypogammaglobulinemia, and lymphocyte abnormalities. Thyroid function and biochemical screening for SDHB-associated tumors were normal. Trio-based whole-exome sequencing identified a\n                      <jats:italic>de novo<\/jats:italic>\n                      pathogenic\n                      <jats:italic>PTEN<\/jats:italic>\n                      variant, c.464A\u2009&amp;gt;\u2009G (p.Tyr155Cys), together with a\n                      <jats:italic>de novo SDHB<\/jats:italic>\n                      variant, c.719T\u2009&amp;gt;\u2009C (p.Leu240Pro). Functional studies showed an increased succinate-to-fumarate ratio and reduced succinate dehydrogenase activity, consistent with impaired mitochondrial complex II function. Structural modeling further suggested that the p.Leu240Pro substitution may reduce SDHB protein stability. Functional evidence fulfilled ACMG\/AMP PS3 criteria and supported the proposed reinterpretation of the\n                      <jats:italic>SDHB<\/jats:italic>\n                      variant from a variant of uncertain significance to likely pathogenic using the OddsPath framework.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This case expands the molecular spectrum of PHTS by describing the coexistence of pathogenic\n                      <jats:italic>PTEN<\/jats:italic>\n                      and functionally supported\n                      <jats:italic>SDHB<\/jats:italic>\n                      variants. Although the phenotype is largely attributable to PHTS, the potential contribution of SDHB dysfunction remains speculative and warrants further investigation. These findings underscore the importance of functional variant interpretation and genotype-informed longitudinal surveillance in rare genetic disorders.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fped.2026.1909252","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:15Z","timestamp":1785217035000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Coexisting PTEN and SDHB Mutations in a Pediatric Patient with PTEN Hamartoma Tumor Syndrome: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Yaqin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Reproductive Genetics, Pu'er People's Hospital","place":["Pu'er, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sooyeon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin P.","family":"Annes","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Endocrinology, Stanford University","place":["Stanford, CA, United States"]},{"name":"Stanford ChEM-H and Endocrine Oncology, Stanford University Cancer Institute","place":["Stanford, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Genetics Department, The First People's Hospital of Yunnan Province","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taicheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Central Lab, Clinical Diagnosis and Treatment Center for Precision Medicine, The Affiliated Hospital of Yunnan University\/Second People's Hospital of Yunnan Province","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Qian","sequence":"additional","affiliation":[{"name":"Central Lab, Clinical Diagnosis and Treatment Center for Precision Medicine, The Affiliated Hospital of Yunnan University\/Second People's Hospital of Yunnan Province","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingli","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University","place":["Kunming, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1754","DOI":"10.1158\/1078-0432.CCR-24-3819","article-title":"Cancer and overgrowth manifestations of PTEN hamartoma tumor syndrome: management recommendations from the international PHTS consensus guidelines working group","volume":"31","author":"Dhawan","year":"2025","journal-title":"Clin Cancer Res"},{"key":"B2","author":"Yehia","year":"2001","journal-title":"PTEN Hamartoma Tumor Syndrome. 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