title: CDC73-related hereditary hyperparathyroidism: five new mutations and the clinical spectrum.
abstract: OBJECTIVE
  Hyperparathyroidism-jaw tumour (HPT-JT) syndrome is a rare autosomal dominant cause of benign and malignant parathyroid tumours, ossifying jaw tumours, various cystic and neoplastic renal abnormalities and benign and malignant uterine tumours. Disease-causing mutations have been localised in the tumour suppressor gene CDC73. There is limited information available on the mutations, and resulting phenotypes and long-term follow-up data are especially scarce.
  
  
  METHODS
  We analysed the clinical data from 16 patients (including three families) carrying mutations in the CDC73 gene. We describe five new mutations/gene variants, the corresponding phenotypes of these carriers and the long-term follow-up.
  
  
  METHODS
  The 16 patients were evaluated at an endocrine outpatient clinic and at a surgical department. DNA samples were obtained for sequence analysis of the CDC73 gene.
  
  
  RESULTS
  Clinical features of HPT-JT syndrome were detected in 13 of the 15 carriers with germline CDC73 mutations. The major features were benign (n=7; 47%) or cancerous (n=3; 20%) HPT-JT was present in eight cases (53%). Most patients had severe hypercalcaemia, and median serum calcium levels were 3.36 mmol/l. A patient with non-secretory parathyroid carcinoma was included. HPT was diagnosed at a median age of 28.5 years. Mutational analysis of the CDC73 gene identified eight sequence changes, three of them have been reported previously, whereas five are novel: c.1346delG, c.88_94delTTCTCCT, the non-coding variants, c.307+5G>T and c.424-5T>C and c.*12C>A of unknown significance.
  
  
  CONCLUSIONS
  This study significantly increases the information available on the mutations and phenotypes of HPT-JT syndrome.
authors.affiliation: Endocrine Practice, Molecular Laboratory, Brückenstr.21, 69120 Heidelberg, Germany. karin.frankraue@raue-endokrinologie.de
authors.forename: Karin
authors.initials: K
authors.lastname: Frank-Raue
authors.forename: Christine
authors.initials: C
authors.lastname: Haag
authors.forename: Egbert
authors.initials: E
authors.lastname: Schulze
authors.forename: Roger
authors.initials: R
authors.lastname: Keuser
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Raue
authors.forename: Henning
authors.initials: H
authors.lastname: Dralle
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lorenz
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010282:Parathyroid Neoplasms / Q000235:genetics*; D010375:Pedigree; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C454900:CDC73 protein, human; D025521:Tumor Suppressor Proteins