Genetic analysis of RET mutations in MEN 2 families from the Community of Murcia, Spain

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) syndromes are inher ited following an autosomal dominant pattern. RET proto-oncogen mutations h ave been associated with MEN 2, The identification of these mutations unabl es us to diagnose MEN 2. The objectives were to recognize RET mutations and gene carriers in the area of Murcia and to sep up the relationship between genotype and phenotype. PATIENTS AND METHODS: 284 subjects from 14 MEN 2A kindreds and one MEN 2B f amily from the Community of Murcia, Spain, were studied. 48 out of them had MEN 2 tumours and 236 subjects were at risk. The initial screening test wa s single-strand conformation polymorphism (SSCP) in 8 MEN 2A families and d enaturing gradient gel electrophoresis (DGGE) in 6 MEN 2A families; the res ults in all the subjects were confirmed with restriction analysis. The MEN 2A family in which the Cfo-I enzyme detected but did not specify the type o f mutation received DNA sequence assay. The MEN 2B kindred was studied with restriction analysis. RESULTS: TGC --> TAC and TGC --> CGC mutations of codon 634 were found in 1 3 and one MEN 2A kindreds, respectively. ATG --> ACG mutation of codon 918 was present in the MEN 2B family. Clinical diagnosis was confirmed in the 4 8 patients, 44 new gene carriers were detected and 192 carriers of normal a lleles were ruled out. The incidence of hyperparathyroidism was highest if RET mutation was TGC --> CGC. CONCLUSIONES: Community of Murcia is one of the areas with the highest prev alence of MEN 2, The risk of hyperparathyroidism is increased if TGC --> CG C is present.