title: FGF23 analysis of a Chinese family with autosomal dominant hypophosphatemic rickets.
abstract: Autosomal dominant hypophosphatemic rickets (ADHR; MIM 193100) is a hereditary disorder characterized by isolated renal phosphate wasting, hypophosphatemia, and inappropriately normal 1,25-dihydroxyvitamin D(3) levels. Recent studies have shown that the fibroblast growth factor 23 (FGF23) gene is responsible for this disease. FGF23 protein is a phosphaturic factor that is elevated in several diseases associated with hypophosphatemia and rickets but varies with disease status in ADHR. In the present study we observed a Chinese family of Han ethnic origin diagnosed with ADHR. The proband is a 30-year-old woman with no history of rickets but with multiple tooth abscesses as a young adult. She presented with progressive painful swelling of the left ankle after a blunt trauma at 26 years of age. She developed back pain, generalized weakness, and fatigue, and she could barely walk at age 27. She was found to have severe hypophosphatemia, low ratio of phosphorus tubule maximum (TmP) to glomerular filtration rate (GFR) (TmP/GFR), and elevated alkaline phosphatase at age 28. Her brother, 26 years old, presented with fatigue at 24 years of age and is normophosphatemic. The parents of this family had no history of rickets or hypophosphatemia. Direct sequence analysis of genomic DNA demonstrated a single heterozygous c.527G>A (p.R176Q) mutation in the FGF23 gene in three family members, including the proband, her brother, and their mother. Intact FGF23 assay of seven time points during the oral phosphate loading test showed no significant relationship between intact FGF23 and serum phosphorus levels of the subject with ADHR and a control. It is probably the first report of a Chinese family with ADHR.
authors.affiliation: Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan No. 1, Wangfujing Dongcheng District, Beijing 100730, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Sun
authors.forename: Ou
authors.initials: O
authors.lastname: Wang
authors.forename: Weibo
authors.initials: W
authors.lastname: Xia
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Xing
authors.forename: Yingying
authors.initials: Y
authors.lastname: Hu
authors.forename: Huaicheng
authors.initials: H
authors.lastname: Liu
authors.forename: Xunwu
authors.initials: X
authors.lastname: Meng
authors.forename: Xueying
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000284:Administration, Oral; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002681:China; D053098:Familial Hypophosphatemic Rickets / Q000097:blood / Q000000981:diagnostic imaging / Q000235:genetics*; D005190:Family; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010375:Pedigree; D010710:Phosphates / Q000008:administration & dosage; D010758:Phosphorus / Q000097:blood; D011859:Radiography
chemical_list: C000717427:FGF23 protein, human; D010710:Phosphates; D010758:Phosphorus; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23