{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T07:52:34Z","timestamp":1773993154986,"version":"3.50.1"},"reference-count":18,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Key Research and Development Program of China","award":["2023YFC2706300"],"award-info":[{"award-number":["2023YFC2706300"]}]},{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of   Hubei Province","doi-asserted-by":"crossref","award":["2025AFB588"],"award-info":[{"award-number":["2025AFB588"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder characterized by hyperphosphatemia and ectopic calcifications. Mutations in GALNT3, which encodes a key enzyme responsible for O-glycosylation of FGF23, represent a major genetic cause of HFTC. This modification is essential for the stability and secretion of FGF23. We investigated a 4-year and 6-month-old Chinese girl with HFTC to characterize the clinical features, identify the causative variants, and explore the underlying pathogenic mechanism. Whole-exome sequencing followed by Sanger validation identified novel compound heterozygous variants in GALNT3 (c.659T&gt;A, p.Ile220Asn and c.1850C&gt;A, p.Ser617*). The patient exhibited hyperphosphatemia with a biochemical profile consistent with FGF23 deficiency, including extremely low intact FGF23 and elevated C-terminal fragments. Functional studies using Western blotting and wheat germ agglutinin affinity chromatography demonstrated that the mutant GALNT3 caused a severe defect in FGF23 O-glycosylation, leading to impaired secretion of intact FGF23. Glycosylated FGF23 was detected only in the medium of cells expressing wild-type GALNT3. These findings indicate that defective O-glycosylation results in failure of FGF23 secretion and functional inactivation. This study expands the mutational spectrum of GALNT3 and provides mechanistic insight into the role of GALNT3 in phosphate homeostasis.<\/jats:p>","DOI":"10.3390\/ijms27062767","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:12:26Z","timestamp":1773853946000},"page":"2767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Functional Characterization of Novel GALNT3 Mutations in a Chinese Child with Hyperphosphatemic Familial Tumoral Calcinosis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7280-7670","authenticated-orcid":false,"given":"Yuan","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shimin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanqin","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3748-4817","authenticated-orcid":false,"given":"Xiaoping","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hubei Provincial Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Hubei Provincial Clinical Research Center for Children\u2019s Growth and Development and Metabolic Diseases, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1038\/ng1358","article-title":"Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis","volume":"36","author":"Topaz","year":"2004","journal-title":"Nat. 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