title: Multiple endocrine neoplasia type 2A in two families with the familial medullary thyroid carcinoma associated G533C mutation of the RET proto-oncogene.
abstract: BACKGROUND
  Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant hereditary disorder, associated with a cluster of germline gain-of-function mutations of the RET proto-oncogene (RET), mainly in exons 10-15. The G533C mutation in exon 8 of the RET is rare and has been mainly related to the familial medullary thyroid carcinoma.
  
  
  METHODS
  We describe the RET G533C mutation in exon 8 of the RET in two unrelated female index patients, with MEN2A phenotype, consisting of pheochromocytoma which was the presenting feature and medullary thyroid carcinoma. In addition, 12 family members were also studied. DNA extraction, PCR, and sequencing of RET was performed in exons 7-19 and 21, following standard procedures.
  
  
  RESULTS
  The mutation was found in both index patients and in 6 out of 12 family members (50%). Three of them were biochemically affected with histologically proven medullary thyroid carcinoma in two of them while there are no certain clues regarding the other three members as they declined further evaluation.
  
  
  CONCLUSIONS
  Patients with MEN2A should be also searched in exon 8 while positive carriers of this mutation should be screened annually for pheochromocytoma or other components of the syndrome.
authors.affiliation: Endocrine Unit, Athens University Medical School, Research Institute and Diabetes Center, Attikon University Hospital, 1 Rimini Street, 12462 Athens, Greece. molypepa@otenet.gr
authors.forename: Melpomeni
authors.initials: M
authors.lastname: Peppa
authors.forename: Eleni
authors.initials: E
authors.lastname: Boutati
authors.forename: Smaragda
authors.initials: S
authors.lastname: Kamakari
authors.forename: Vasilios
authors.initials: V
authors.lastname: Pikounis
authors.forename: George
authors.initials: G
authors.lastname: Peros
authors.forename: Ioannis G
authors.initials: IG
authors.lastname: Panayiotides
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
authors.forename: Sotirios A
authors.initials: SA
authors.lastname: Raptis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Hadjidakis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution / Q000235:genetics; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000473:pathology; D003545:Cysteine / Q000235:genetics; D005260:Female; D005998:Glycine / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics*; D013577:Syndrome; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D003545:Cysteine; D005998:Glycine