title: Presence of the RET Cys634Tyr mutation and Gly691Ser functional polymorphism in Iranian families with multiple endocrine neoplasia type 2A.
abstract: OBJECTIVE
  Multiple Endocrine Neoplasia type 2A (MEN2A) is a complex autosomal dominant inherited syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and primary parathyroid hyperplasia. In patients with only one or two clinical features, identification of a germ line RET (REarranged in Transfection) mutation is required to make the diagnosis and initiate genetic counseling.
  
  
  METHODS
  We analyzed blood DNA from three Iranian families with three generations of MEN2A including 20 affected individuals with MTC and four with pheochromocytoma. RET hotspots were amplified in probands and sequenced for mutation detection.
  
  
  RESULTS
  The causative mutation in all families was found to be the Cys634Tyr missense substitution. The presence of a functional SNP resulting in Gly691Ser was also detected in exon 11 of 15 affected cases. Four patients showed both of these RET variations.
  
  
  CONCLUSIONS
  Our study shows that the Cys634Tyr missense substitution and the Gly691Ser polymorphism are recurrent in Iranian patients, since our families are unrelated. All asymptomatic carriers of the Cys634Tyr high-risk activating mutation were referred for prophylactic thyroidectomy.
authors.affiliation: Medical Genetics Research Center, Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Maryam Nasiri
authors.initials: MN
authors.lastname: Aghdam
authors.affiliation: Division of Human Genetics, Immunology Research Center, Avicena Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Abbaszadegan
authors.affiliation: Medical Genetics Research Center, Department of Medical Genetics, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Tafazoli
authors.affiliation: Endocrine Research Center, Imam Reza/Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences; Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Aslzare
authors.affiliation: Endocrine Research Center, Imam Reza/Ghaem Hospital, School of Medicine, Mashhad University of Medical Sciences; Mashhad, Iran.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Mosavi
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics; D000328:Adult; D018276:Carcinoma, Medullary / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007492:Iran / Q000453:epidemiology; D008297:Male; D018813:Multiple Endocrine Neoplasia Type 2a / Q000453:epidemiology / Q000235:genetics*; D010375:Pedigree; D010673:Pheochromocytoma / Q000235:genetics; D011110:Polymorphism, Genetic; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000235:genetics
chemical_list: D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human