Parent-of-origin effects in multiple endocrine neoplasia type 2B

Am J Hum Genet. 1994 Dec;55(6):1076-82.


Multiple endocrine neoplasia type 2B (MEN 2B) is characterized by medullary thyroid carcinoma, pheochromocytomas, mucosal neuromas, ganglioneuromas, and skeletal and ophthalmic abnormalities. It is observed as both inherited and sporadic disease, with an estimated 50% of cases arising de novo. A single point mutation in the catalytic core region of the receptor tyrosine kinase, RET, has been observed in germ-line DNA of MEN 2B patients. We have analyzed 25 cases of de novo disease in order to determine the parental origin of the mutated RET allele. In all cases the new mutation was of paternal origin. We observe a distortion of the sex ratio in both de novo MEN 2B patients and the affected offspring of MEN 2B transmitting males. These results suggests a differential susceptibility of RET to mutation in paternally and maternally derived DNA and a possible role for imprinting of RET during development.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Chromosomes, Human, Pair 10
  • Drosophila Proteins*
  • Female
  • Flow Cytometry
  • Genetic Markers
  • Genotype
  • Humans
  • Hybrid Cells
  • Male
  • Meiosis
  • Multiple Endocrine Neoplasia Type 2b / etiology
  • Multiple Endocrine Neoplasia Type 2b / genetics*
  • Mutation*
  • Pedigree
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Sex Ratio
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / genetics


  • Drosophila Proteins
  • Genetic Markers
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila