Endocrine Abstracts

Multiple endocrine neoplasia type2 (MEN 2) (OMIM 171400) is an autosomal dominant inherited cancer syndrome caused by activating mutations in the RET proto-oncogene. MEN 2 is classified into three subtypes: MEN 2A, MEN 2B and familial medullary thyroid carcinoma(FMTC). MEN 2B accounts for 5–10% of MEN2 cases. More than 95% of MEN 2B patients carry M918T mutation of RET, and 2–3% harbor A883F mutation. There has been three reports of cases with MEN 2B phenotype caused by double RET missense mutations of codons 805], 806and 904 in cis with V804M mutation. The V804M/Y806C mutations were the first case reported in a patient with MEN 2B like phenotype, functional tests of which suggest that the transforming activity of this double mutation was similar to that of the M918T defect.

Clinical case: A 32-year-old female presented with neck mass. She had had bumpy lips and multiple nodules on her lips, tongue, buccal mucosa and conjunctiva since childhood, but besides that she had been in good health. There was no family history of endocrine diseases. Fine-needle aspiration biopsy showed the characters of medullary cell carcinoma of the thyroid with lymphmetastasis. Histopathological examination of the buccal mucosa nodule showed multiple dermal nodules which was diagnosed as schwanoma. The serum calcitonin level was 6080pg/ml, and caricinoembryonic antigen levels was 435.2ng/ml. A total thyroidectomy was performed with central and right radical neck lymph node dissection.

Mutation analysis of the RET gene: The proband’s genomic DNA was extracted from the blood samples and was screened for mutations in exons 10, 11, and 13–16 of the RET gene by the PCR-direct sequencing analysis. We detected two heterozygous missense mutations V804M and Q781R. Subcloning analysis of the gene revealed that the both mutations were present on the same allele. The genotype of her parents were examined under their informed consent. Q781R mutation was found in her father, and no mutation was found in her mother.

Discussion: We have identified a novel combination of RET missense mutation, V804M and Q781R. Subclone analysis had demonstrated that the de novo V804M mutation is on the paternal allele. Although several double mutation cases have been reported to cause MEN2B, the combination of the present case has not been reported.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.