{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:26:45Z","timestamp":1786976805021,"version":"build-2736575974"},"reference-count":14,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,7]]},"abstract":"ABSTRACT<\/jats:title>\n \n Maple syrup urine disease (MSUD) is a rare inborn error of metabolism caused by impaired catabolism of branched\u2010chain amino acids (BCAAs). The genes\n BCKDHA<\/jats:italic>\n ,\n BCKDHB<\/jats:italic>\n ,\n DBT<\/jats:italic>\n , and\n DLD<\/jats:italic>\n encode the subunits of the branched\u2010chain \u03b1\u2010ketoacid dehydrogenase (BCKDH) complex, which is essential for BCAA metabolism. Catalytic subunits are\n BCKDHA<\/jats:italic>\n ,\n BCKDHB<\/jats:italic>\n ,\n DBT<\/jats:italic>\n , and\n DLD<\/jats:italic>\n , whereas the regulator subunits are\n PPM1K<\/jats:italic>\n and\n BCKDK<\/jats:italic>\n .\n PPM1K<\/jats:italic>\n plays a critical role by dephosphorylating and activating this enzyme complex. Pathogenic variants in the\n PPM1K<\/jats:italic>\n gene cause an extremely rare, mild form of MSUD. Here, we report an 8\u2010year\u2010old male patient with a mild form of MSUD putatively caused by a novel homozygous variant in\n PPM1K<\/jats:italic>\n . The patient presented with mild dysmorphic features, delayed speech, relative microcephaly, and overweight, all considered familial phenotypic traits. Laboratory findings revealed mildly elevated plasma branched\u2010chain amino acids, mild lactic acidemia, and a slight increase in urinary keto acids. Exome sequencing identified a novel homozygous missense variant, c.925A>G p.(Ile309Val), in the\n PPM1K<\/jats:italic>\n gene. This case represents the third reported patient with a mild form of MSUD associated with the first reported missense variant in the\n PPM1K<\/jats:italic>\n gene in the literature, further expanding the clinical and genetic spectrum of PPM1K\u2010related disorders.\n <\/jats:p>","DOI":"10.1002\/ajmg.a.64037","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T18:56:08Z","timestamp":1741719368000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Expanding the Genetic Spectrum of\n PPM1K<\/scp>\n \u2010Related Maple Syrup Urine Disease: A Novel Mutation"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1401-5233","authenticated-orcid":false,"given":"Mustafa","family":"K\u0131l\u0131\u00e7","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Metabolism Unit Ankara Etlik City Hospital, University of Health Sciences Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4147-3383","authenticated-orcid":false,"given":"Esra","family":"Sayar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Metabolism Unit Ankara Etlik City Hospital Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7212-6866","authenticated-orcid":false,"given":"Suzan","family":"\u0130cil","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Metabolism Unit Ankara Etlik City Hospital Ankara Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4412-6732","authenticated-orcid":false,"given":"Sevgi","family":"Do\u011fan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Metabolism Unit Ankara Etlik City Hospital Ankara 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Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3886-3808","authenticated-orcid":false,"given":"Abdullah","family":"Sezer","sequence":"additional","affiliation":[{"name":"Department of Genetics Ankara Etlik City Hospital Ankara 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