Genetic testing for multiple endocrine neoplasia type 2

Rom J Intern Med. 2008;46(2):159-63.

Abstract

Multiple endocrine neoplasia type 2 (MEN 2) represents a complex autosomal dominant inherited syndrome characterized by occurrence of distinct proliferative disorders of endocrine tissues. The identification of RET proto-oncogene mutations in MEN 2 and FMCT has provided a precise method for identifying gene carriers. 30 subjects (9 males, 21 females, age range 11-63 years) with multiple endocrine neoplasia type 2 have been investigated from 1998 till 2006. 20 patients were considered as index cases and 10 patients were identified after a screening programme for MEN 2. Tumoral associations permitted the MEN 2A diagnosis in 21 cases, MEN 2A with cutaneous lichen amyloidosis in 6 cases and FMCT in 3 cases. We selected 22 patients from 14 families to investigate mutations in the RET proto-oncogene. In 7 subjects no mutations could be detected in the exons 10 and 11 of the RET proto-oncogene. Heterozygous missense mutations in exon 11 were found in 15 subjects consisting of three different mutations in codon 634 (TGC --> TGG, TGC --> GGC, TGC --> CGC). We conclude that our 15 patients have the most frequent mutations described in MEN 2A families. Because the testing for exons 10 and 11 is negative for other 7 patients, the remaining 13, 14, 15 and 16 exons should be sequenced in these cases.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Codon / genetics
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Genetic Carrier Screening
  • Genetic Testing*
  • Humans
  • Male
  • Middle Aged
  • Multiple Endocrine Neoplasia Type 2a / diagnosis*
  • Multiple Endocrine Neoplasia Type 2a / genetics*
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Mutation, Missense / genetics*
  • Polymerase Chain Reaction
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret / genetics*
  • Reproducibility of Results
  • Retrospective Studies
  • Young Adult

Substances

  • Codon
  • MAS1 protein, human
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-ret
  • RET protein, human