[Genetic analysis of RET mutations in families with multiple endocrine neoplasia type II in the community of Murcia].
BACKGROUND
Multiple endocrine neoplasia type 2 (MEN 2) syndromes are inherited following an autosomal dominant pattern. RET protooncogen mutations have been associated with MEN 2. The identification of these mutations enables 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.


METHODS
284 subjects from 14 MEN 2A kindreds and one MEN 2B family 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 was single-strand conformation polymorphism (SSCP) in 8 MEN 2A families and denaturing gradient gel electrophoresis (DGGE) in 6 MEN 2A families; the results 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 of 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 13 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 48 patients, 44 new gene carriers were detected and 192 carriers of normal alleles were ruled out. The incidence of hyperparathyroidism was highest if RET mutation was TGC-->CGC.


CONCLUSIONS
Community of Murcia is one of the areas with the highest prevalence of MEN 2. The risk of hyperparathyroidism is increased if TGC-->CGC is present.
Pomares Gómez
F J
FJ
Sección de Endocrinología y Nutrición, Hospital Universitario Virgen de la Arrixaca, Murcia.
Bernabé Espinosa
M J
MJ
Matías-Guiu Guía
X
X
Rodríguez González
J M
JM
Soriano Palao
J
J
Sola Pérez
J
J
Carbonell Meseguer
P
P
Parrilla Paricio
P
P
Tébar Massó
F J
FJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D018276:Carcinoma, Medullary / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003062:Codon; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004262:DNA Restriction Enzymes / Q000235:genetics; D004587:Electrophoresis, Agar Gel / Q000379:methods; D005091:Exons; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D006961:Hyperparathyroidism / Q000453:epidemiology / Q000235:genetics; D007223:Infant; D008297:Male; D008875:Middle Aged; D018814:Multiple Endocrine Neoplasia Type 2b / Q000453:epidemiology / Q000235:genetics*; D009691:Nucleic Acid Denaturation / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D010673:Pheochromocytoma / Q000453:epidemiology / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015995:Prevalence; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D013030:Spain / Q000453:epidemiology; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*
D003062:Codon; D017931:DNA Primers; D011518:Proto-Oncogene Proteins; D004262:DNA Restriction Enzymes
Análisis genético de las mutaciones de RET en las familias con neoplasia endocrina múltiple tipo 2 de la Comunidad de Murcia.