Multiple endocrine neoplasia type 2A due to an exon 8 (G533C) mutation in a large north American kindred

M. Regina Castro, Brittany C. Thomas, Melanie L. Richards, Jun Zhang, John C. Morris

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Background: Medullary thyroid cancer, although most commonly sporadic, may be part of the multiple endocrine neoplasia type 2 (MEN2) syndromes, generally due to mutations in the RET proto-oncogene. The majority of these mutations are located in exons 10, 11, and 13-16. More rarely, mutations in other exons have been described. We report for the first time a family from the United States with a rare mutation involving exon 8 of the RET proto-oncogene, corresponding to a p.Gly533Cys substitution (G533C) leading to the development of MEN2A syndrome in several affected family members. This mutation had only been previously described in a large family in Brazil and in 7.75% of patients with apparently sporadic medullary thyroid cancer (MTC) in Greece. Methods: Given a strong index of suspicion, a genetic analysis to evaluate for uncommon mutations in the RET proto-oncogene identified the presence of the G533C missense mutation, despite initial negative screening for common mutations. We describe a family with a total of 47 individuals from five generations with multiple members affected with this mutation. Results: Our data suggest that in patients with this mutation, pheochromocytoma is more common than previously reported, and that in some cases this mutation may be associated with a more aggressive phenotype than initially described. Conclusions: MEN2A due to the G533C mutation in exon 8 may be more common and more aggressive than previously recognized. In patients with medullary thyroid cancer with negative screening for common mutations in the RET oncogene but a strong index of suspicion, DNA sequence analysis of less commonly involved exons should be considered.

Original languageEnglish (US)
Pages (from-to)1547-1552
Number of pages6
JournalThyroid
Volume23
Issue number12
DOIs
StatePublished - Dec 1 2013

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Multiple Endocrine Neoplasia Type 2a
Exons
Mutation
Proto-Oncogenes
Multiple Endocrine Neoplasia
Greece
Pheochromocytoma
Missense Mutation
DNA Sequence Analysis
Oncogenes
Brazil

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Endocrinology

Cite this

Multiple endocrine neoplasia type 2A due to an exon 8 (G533C) mutation in a large north American kindred. / Castro, M. Regina; Thomas, Brittany C.; Richards, Melanie L.; Zhang, Jun; Morris, John C.

In: Thyroid, Vol. 23, No. 12, 01.12.2013, p. 1547-1552.

Research output: Contribution to journalArticle

Castro, M. Regina ; Thomas, Brittany C. ; Richards, Melanie L. ; Zhang, Jun ; Morris, John C. / Multiple endocrine neoplasia type 2A due to an exon 8 (G533C) mutation in a large north American kindred. In: Thyroid. 2013 ; Vol. 23, No. 12. pp. 1547-1552.
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