title: Direct, non-radioactive detection of mutations in multiple endocrine neoplasia type 2A families.
abstract: We have designed PCR primers that permit the rapid non-isotopic detection of mutations in codon 634 of the RET proto-oncogene, the causative mutations in over 80% of MEN 2A and 50% of FMTC families. In this paper we report the investigation of eleven MEN 2A families referred to the East Anglian Regional Genetics Service. Nine of these families carry codon 634 mutations. We were able to confirm the diagnosis of MEN 2A in twenty six affected individuals and to determine the carrier status of forty one individuals thought to be at risk of developing the disease. Of those at risk, thirty one patients lacked the familial mutation and ten were presymptomatic carriers of MEN 2A. In five cases the direct test proved that patients who had been treated by thyroidectomy but who lacked confirmed cancer, did not carry the familial mutation, removing the perceived risk of MEN 2A from their children. This group included one patient who had been diagnosed as having mild C-cell hyperplasia, confirming that in MEN 2A families C-cell hyperplasia can result from causes other than the presence of the MEN 2A mutation.
authors.affiliation: East Anglian Regional Genetics Service, Molecular Genetics Laboratory, Addenbrooke's NHS Trust, Cambridge, UK.
authors.forename: R
authors.initials: R
authors.lastname: McMahon
authors.forename: L M
authors.initials: LM
authors.lastname: Mulligan
authors.forename: C S
authors.initials: CS
authors.lastname: Healey
authors.forename: S J
authors.initials: SJ
authors.lastname: Payne
authors.forename: M
authors.initials: M
authors.lastname: Ponder
authors.forename: M A
authors.initials: MA
authors.lastname: Ferguson-Smith
authors.forename: D E
authors.initials: DE
authors.lastname: Barton
authors.forename: B A
authors.initials: BA
authors.lastname: Ponder
mesh_terms: D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000097:blood; D002116:Calcitonin / Q000097:blood; D018276:Carcinoma, Medullary / Q000097:blood / Q000235:genetics / Q000601:surgery; D002648:Child; D003062:Codon; D004252:DNA Mutational Analysis; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D005260:Female; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008969:Molecular Sequence Data; D009377:Multiple Endocrine Neoplasia / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000097:blood / Q000235:genetics; D010375:Pedigree; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012306:Risk; D013961:Thyroid Gland / Q000473:pathology; D013964:Thyroid Neoplasms / Q000097:blood / Q000235:genetics / Q000601:surgery; D013965:Thyroidectomy
chemical_list: D014408:Biomarkers, Tumor; D003062:Codon; D017931:DNA Primers; D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D002116:Calcitonin; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila