C618R mutation in exon 10 of the RET proto-oncogene in a kindred with multiple endocrine neoplasia type 2A and Hirschsprung's disease

J Clin Endocrinol Metab. 1996 Jul;81(7):2731-3. doi: 10.1210/jcem.81.7.8675603.

Abstract

The cosegregation of multiple endocrine neoplasia (MEN) type 2A with Hirschsprung's disease (HSCR), two diseases associated with mutation of the RET proto-oncogene, is infrequent. A 30-yr-old man was referred for screening of MEN 2A. Surgery for HSCR was performed at 4 yr of age. Basal and pentagastrin-stimulated calcitonin levels were abnormal. Histological examination of the thyroid confirmed bilateral medullary thyroid carcinoma. Screening of family members revealed six subjects with medullary thyroid carcinoma or abnormal pentagastrin-stimulated calcitonin test; one had an unilateral pheochromocytoma and two were affected with HSCR. DNA sequence analysis showed a heterozygote C618R mutation in exon 10 of the RET proto-oncogene in the proband and his mother, as well as in second-degree relatives with MEN 2A phenotype or HSCR. In this study, we report on a novel kindred with MEN 2A and HSCR phenotype associated with a point mutation (C618R) in one of the cysteine codons at the extracellular domain of the RET proto-oncogene.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Calcitonin / metabolism
  • Carcinoma, Medullary / pathology
  • Drosophila Proteins*
  • Exons
  • Female
  • Hirschsprung Disease / complications
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Multiple Endocrine Neoplasia Type 2a / complications
  • Multiple Endocrine Neoplasia Type 2a / genetics*
  • Multiple Endocrine Neoplasia Type 2a / pathology
  • Mutation*
  • Pedigree
  • Pentagastrin
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Thyroid Neoplasms / pathology

Substances

  • Drosophila Proteins
  • Proto-Oncogene Proteins
  • Calcitonin
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • Pentagastrin