Evidence for the founder effect of RET533 as the common Greek and Brazilian ancestor spreading multiple endocrine neoplasia 2A.

Objectives: About one-quarter of patients with medullary thyroid cancer (MTC) have inherited disease due to mutations in the gene. A rare mutation in exon 8 (G533C) of , previously described in a large Brazilian family with MEN2A, also appeared to be clustering in Greece, whereas it was rarely reported in other ethnic groups. The aim of this study was to identify a possible common ancestry between these carriers.

Genome-wide copy number analysis in a family with p.G533C RET mutation and medullary thyroid carcinoma identified regions potentially associated with a higher predisposition to lymph node metastasis.

Context: Our group described a p.G533C RET gene mutation in a large family with multiple endocrine neoplasia type 2 syndrome. Clinical heterogeneity, primarily associated with the presence of lymph node metastases, was observed among the p.

A ten-year clinical update of a large RET p.Gly533Cys kindred with medullary thyroid carcinoma emphasizes the need for an individualized assessment of affected relatives.

Objective: Reviewing the clinical outcomes of a large kindred with a RET p.Gly533Cys mutation, 10 years after the first description of this kindred, has provided an important set of clinical data for healthcare decision-making.

Design And Patients: We identified 728 RET533 Brazilian relatives, spread out over 7 generations.