J Korean Endocr Soc.  2007 Dec;22(6):453-459. 10.3803/jkes.2007.22.6.453.

A Family of Multiple Endocrine Neoplasia Type 2A with a C634R Mutation and a G691S Polymorphism in RET Proto-oncogene

• Yun SW
• Yoo WS
• Hong KH
• Kim BH
• Kang MH
• Choo YK
• Park HY
• Kim DH
• Chung HK
• Chang MC
• Kwon MS
• Kim HJ

• KMID: 1958911
• DOI: http://doi.org/10.3803/jkes.2007.22.6.453

Abstract

Multiple endocrine neoplasia type 2A (MEN2A) is an autosomal dominant syndrome characterized by the presence of a medullary thyroid carcinoma, pheochromocytoma and hyperparathyroidism. MEN2A arises due to germline missense mutations of the RET proto-oncogene. Specific RET mutations correlate with the onset of age and the aggressiveness of a medullary thyroid carcinoma. However, the clinical presentation varies even within families, where patients carry the same mutation. Recently, it has been reported that polymorphisms of RET may have a modifier effect on the presentation. We experienced a case of 42-year-old man, whose bilateral pheochromocytoma and medullary thyroid carcinoma were incidentally found. Genetic testing detected a mutation in codon 634 (C634R) and a polymorphism in codon 691 (G691S) of the RET proto-oncogene. His mother, younger brother and his only son had the same mutation and polymorphism. We report this case with a review of the literature about RET gene polymorphisms.

Keyword

multiple endocrine neoplasia type 2A; polymorphism; RET proto-oncogene

MeSH Terms

Adult
Codon
Genetic Testing
Humans
Hyperparathyroidism
Mothers
Multiple Endocrine Neoplasia Type 2a*
Multiple Endocrine Neoplasia*
Mutation, Missense
Pheochromocytoma
Proto-Oncogenes*
Siblings
Thyroid Neoplasms
Codon

Figure

• 

  Fig. 1 Adrenal CT scan shows huge mass in both adrenal glands (A). I-131 MIBG scan shows bilateral adrenal uptake with no evidence of metastasis (B). Ultrasound sonogram shows heterogeneous hyperechogenic solid nodules with dense calcification and posterior acoustic shadowing in the both thyroid (C).

• 

  Fig. 2 Histologic features of pheochromocytoma (A). It shows predominantly alveolar (zellballen) arrangement tumor cells and the prominent capillary network around each group of cells. The tumor cells show granular and basophilic cytoplasm. Cellular and nuclear pleomorphism is indistinct (H&E stain, ×400). Histologic features of the medullary thyroid carcinoma (B). The tumor shows predominantly solid growth pattern and is intersected by fibrous and amyloid deposits. Tumor cells contain round to oval, regular nuclei with coarse chromatin (H&E stain, ×400).

• 

  Fig. 3 Genetic testing detected a mutation in codon 634 (C634R) and a polymorphism in codon 691 (G691S) of the RET proto-oncogene.

• 

  Fig. 4 The family tree shows 4 members with a mutation in codon 634 (C634R) and a polymorphism in codon 691 (G691S) of the RET proto-oncogene. Arrow indicates proband.

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