It seems that this mutation causes FMTC as no other mutation was found in the classical risk exons (10, 11, 13, 14, 15 and 16) of the RET proto-oncogene.
The variants were observed only in the DNA of individuals who were either affected or who had inherited the MEN2A or FMTC allele as determined by haplotyping experiments.
ATA guidelines that includes risk assessment of RET mutation are important in predicting the presence of MTC in patients who are candidates for prophylactic thyroidectomy and in determining the timing of operative resection.
The effective management of patients with MEN2A, MEN2A, and FMTC depends on an understanding of the variable behavior of disease expression in patients with a specific RET mutation.
Genetic screening for germline RET proto-oncogene mutation in hereditary medullary thyroid cancer (MTC) is accurate and allows for preventive total thyroidectomy to be performed early in patients who are gene carriers.
Recently specific point mutations of RET have been demonstrated to be responsible for the Multiple Endocrine Neoplasia type 2A and 2B and Familial Medullary Thyroid Carcinoma syndromes, characterized by the occurrence of medullary thyroid carcinomas.
We investigated the transforming activity of the ret proto-oncogene with a mutation in cysteine 609, 611, 618, 620, 630, or 634 detected in patients with multiple endocrine neoplasia type 2A (MEN 2A), familial medullary thyroid carcinoma (FMTC), or Hirschsprung's disease.
Polyphen-2 Hum Div/Var may provide additional clinical data to help distinguish benign from MEN2/familial medullary thyroid carcinoma-causing RET variants as well as less aggressive phenotypes (ATA A) from more aggressive ones (ATA B-C).
Identification of the RET mutation in the Dutch population with hereditary C-cell carcinoma facilitates genetic testing for families or individuals at risk for MEN 2A, FMTC, and MEN 2B.
Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfectionCys620Arg mutation.
Mutations in the RET proto-oncogene have been identified in the constitutional DNA of patients with the inherited disorders multiple endocrine neoplasia type 2A and 2B and familial medullary thyroid carcinoma.
Altogether, we and others found 21 missense mutations in five cysteines clustered in the extra-cellular domain of RET (exons 10 and 11) associated with 111 MEN 2A and FMTC families.
In conclusion, familial medullary thyroid carcinoma with noncysteine RET mutations are not infrequent and are overrepresented in presumed sporadic medullary thyroid carcinoma, suggesting that RET analysis should routinely be extended to exons 13, 14, and 15.
Germline missense point mutations of the ret proto-oncogene have been shown as causative in multiple endocrine neoplasia type 2 (MEN 2A and 2B) and in familial medullary thyroid carcinoma (FMTC).
Presentation of a kindred with familial medullary thyroid carcinoma and Cys611Phe mutation of the RET proto-oncogene demonstrating low grade malignancy.