Coincidence of multiple endocrine neoplasia types 1 and 2: mutations in the RET protooncogene and MEN1 tumor suppressor gene in a family presenting with recurrent primary hyperparathyroidism.
BACKGROUND
Primary hyperparathyroidism (HPT) presents as a part of inherited syndromes such as multiple endocrine neoplasia (MEN) types 1 and 2. In patients with MEN1, parathyroid hyperplasia or multiple adenomas occur in approximately 90-95%. MEN2A-related HPT is characterized by a mild hypercalcemia, which is mostly asymptomatic.


OBJECTIVE
Here we present a family with coexistence of MEN1 gene mutation and RET mutation.


RESULTS
Six family members carrying MEN1 gene mutation IVS5 + 1G>A only, one family member with RET mutation Y791F, and three family members with both MEN1 gene and RET mutation were studied. The key to diagnosis was recurrent HPT in a young male carrying RET mutation Y791F, a mutation not likely to give rise to recurrent HPT.


CONCLUSIONS
MEN1 gene mutation and RET codon 791 mutation in the same patient did not affect the typical phenotype of MEN1 or MEN2, and also the course of diseases seems to be unchanged. The reason may be that both mutations, although contributing to tumor pathogenesis, do not interact and induce a worsening of the cancer syndromes.
Frank-Raue
Karin
K
karin.frankraue@raue-endokrinologie.de
Rondot
Susanne
S
Hoeppner
Wolfgang
W
Goretzki
Peter
P
Raue
Friedhelm
F
Meng
Wieland
W
D000328:Adult; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D006961:Hyperparathyroidism / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018761:Multiple Endocrine Neoplasia Type 1 / Q000235:genetics*; D018813:Multiple Endocrine Neoplasia Type 2a / Q000235:genetics*; D018814:Multiple Endocrine Neoplasia Type 2b / Q000235:genetics*; D009154:Mutation; D015513:Oncogene Proteins / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012008:Recurrence
C105373:MEN1 protein, human; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases