title: Transforming growth factor-β1 gene mutations and phenotypes in pediatric patients with Camurati‑Engelmann disease.
abstract: The aim of the present study was to investigate the clinical characteristics and major causative gene in pediatric patients with Camurati‑Engelmann disease (CED). Biochemical and radiographic examinations, bone scintigraphy and genetic analyses were performed in two affected males and their parents. The two patients experienced waddling gait, muscular weakness and growth developmental delay. X-ray radiography revealed typical fusiform thickening of the diaphyseal portions of the long bones. The abnormal uptake of tracer Tc-99m was visualized in the skull and both sides of the upper humeri, ulnas, radii, femurs and tibias using bone scintigraphy. Serum levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) and the bone resorption marker β‑isomerized C-terminal cross-linked telopeptide of type I collagen (β-CTX) in the 6-year-old patient were significantly increased compared with the normal value range, while only the β-CTX levels were elevated in the 16-year-old patient. A heterozygous missense mutation p.Arg218Cys in exon 4 of the transforming growth factor β1 (TGFβ1) gene was detected in the two patients, while their parents had normal wild‑type genotypes. In conclusion, the p.Arg218Cys mutation was shown to contribute to the clinical phenotypes in two pediatric patients with CED. The results of this study suggest that abnormal bone turnover marker levels, typical radiological findings and mutations in the TGFβ1 gene are three important factors in the diagnosis of sporadic CED cases.
authors.affiliation: Department of Osteoporosis and Bone Diseases, Metabolic Bone Disease and Genetics Research Unit, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, PR China.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Bao-Hong
authors.initials: BH
authors.lastname: Zhang
authors.forename: Yu-Juan
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yun-Qiu
authors.initials: YQ
authors.lastname: Hu
authors.forename: Jin-Wei
authors.initials: JW
authors.lastname: He
authors.forename: Zhen-Lin
authors.initials: ZL
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density; D016723:Bone Remodeling; D003966:Camurati-Engelmann Syndrome / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D002648:Child; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology; D020022:Genetic Predisposition to Disease; D006615:Hip / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011859:Radiography; D011877:Radionuclide Imaging; D053773:Transforming Growth Factor beta1 / Q000235:genetics*
chemical_list: D015415:Biomarkers; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1