{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:04:50Z","timestamp":1760058290107,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010731","name":"Chiang Mai University","doi-asserted-by":"publisher","award":["76-2565","B13F660074","HSRI67-137"],"award-info":[{"award-number":["76-2565","B13F660074","HSRI67-137"]}],"id":[{"id":"10.13039\/501100010731","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NSRF via the Program Management Unit for Human Resources &amp; Institutional Development, Research and Innovation","award":["76-2565","B13F660074","HSRI67-137"],"award-info":[{"award-number":["76-2565","B13F660074","HSRI67-137"]}]},{"name":"Genomic Thailand Project of the Health Systems Research Institute, Thailand","award":["76-2565","B13F660074","HSRI67-137"],"award-info":[{"award-number":["76-2565","B13F660074","HSRI67-137"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phosphatidylinositol glycan class T (PIGT) is part of the glycosylphosphatidylinositol transamidase (GPI-TA) complex, crucial for various cell functions. Biallelic pathogenic variants in PIGT are associated with Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 (MCAHS3), a rare neonatal hypotonia syndrome characterized by dysmorphic features and seizures. Diagnosing neonatal hypotonia, which has diverse congenital and acquired causes, is challenging, particularly in syndromic monogenic cases. Next-generation sequencing is essential for accurate diagnosis. This study reports a term newborn with hypotonia, dysmorphic features, seizures, and severe skeletal issues, including a humeral fracture at birth, consistent with MCAHS3. Trio whole exome sequencing (WES) analysis revealed a novel homozygous missense variant in PIGT, expanding the clinical spectrum of MCAHS3 and marking the first such case in the Thai population. The identified c.257A&gt;G (p.His86Arg) variant manifests a severe MCAHS3 phenotype, as evidenced by reduced CD59 expression in western blot analysis, indicating impaired GPI-AP synthesis. Computational predictions suggest this mutation causes protein instability, potentially affecting GPI anchor attachment. While alkaline phosphatase (ALP), a GPI-AP crucial for skeletal mineralization, was elevated in this case, suggesting a late-stage GPI synthesis defect. The His86Arg mutation in PIGT may disrupt GPI-TA function, hindering proper protein attachment and leading to cleaved protein secretion. Further functional studies are needed to elucidate the impact of this mutation on PIGT function and MCAHS3 phenotypes.<\/jats:p>","DOI":"10.3390\/ijms26062790","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T05:03:59Z","timestamp":1742447039000},"page":"2790","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Novel Homozygous Missense Variant of PIGT Related to Multiple Congenital Anomalies-Hypotonia Seizures Syndrome 3 with Elevated of Serum ALP Level in a Thai Newborn Patient"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4992-5296","authenticated-orcid":false,"given":"Jeerawan","family":"Klangjorhor","sequence":"first","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Office of Research Administration, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Musculoskeletal Science and Translational Research (MSTR), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3368-2330","authenticated-orcid":false,"given":"Natrujee","family":"Wiwattanadittakul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanapak","family":"Jaimalai","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5392-9062","authenticated-orcid":false,"given":"Patcharawadee","family":"Thongkumkoon","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5351-9998","authenticated-orcid":false,"given":"Pitiporn","family":"Noisagul","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ratchadaporn","family":"Khiaomai","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nutnicha","family":"Sirikaew","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nonthanan","family":"Moonsan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-8003","authenticated-orcid":false,"given":"Arnat","family":"Pasena","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pathacha","family":"Suksakit","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pimpisa","family":"Teeyakasem","sequence":"additional","affiliation":[{"name":"Musculoskeletal Science and Translational Research (MSTR), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0047-5578","authenticated-orcid":false,"given":"Parunya","family":"Chaiyawat","sequence":"additional","affiliation":[{"name":"Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Musculoskeletal Science and Translational Research (MSTR), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maliwan","family":"Tengsujaritkul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1194\/jlr.R063313","article-title":"Biosynthesis of GPI-anchored proteins: Special emphasis on GPI lipid remodeling","volume":"57","author":"Kinoshita","year":"2016","journal-title":"J. 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