Mutation screening of RET proto-oncogene in a family with medullary thyroid carcinoma, marfanoid habitus and pheochromoc
- PDF / 150,114 Bytes
- 2 Pages / 595.276 x 790.866 pts Page_size
- 62 Downloads / 180 Views
LETTER TO THE EDITOR
Mutation screening of RET proto-oncogene in a family with medullary thyroid carcinoma, marfanoid habitus and pheochromocytoma; from clinically MEN2B to genetically MEN2A syndrome Shirin Hasani-Ranjbar • Mahsa M. Amoli
Published online: 31 January 2012 Ó Springer Science+Business Media, LLC 2012
Multiple endocrine neoplasia type 2 (MEN2) is sub-classified into three syndromes: MEN2A; MEN2B; and familial medullary thyroid cancer (FMTC). MEN2A is characterized by pheochromocytoma, medullary thyroid carcinoma (MTC), and hyperparathyroidism because of primary parathyroid hyperplasia. MEN2B shares the inherited predisposition to MTC and pheochromocytoma that occurs in MEN2A. However, MEN2B patients typically have a marfanoid habitus (but do not have Marfan’s syndrome), mucosal neuromas (typically involving the lips and tongue), and intestinal ganglioneuromatosis. Pheochromocytoma in MEN 2A is associated most frequently with mutations in codon 634 (in exon 11). Subjects with this have a more than 90, 50, and 30% probability of developing medulary thyroid cancer, pheochromocytoma, and hyperparathyroidism, respectively. MEN 2B is associated with mutations primarily in codon 918 (in exon 16) of the RET proto-oncogene [1, 2]. Differentiation between MEN2A and MEN2B is critical for management of such patients, since, in MEN2A, prophylactic thyroidectomy is recommended to be performed in carriers later. In patients with MEN2B, MTC is often more aggressive and of earlier onset than in MEN2A. We report here a family in which the index patient had marfanoid habitus, MTC, and bilateral pheochromocytoma which is clinically supposed to be matched with MEN2B and finally diagnosed as MEN2A according to genetic tests.
S. Hasani-Ranjbar (&) M. M. Amoli Endocrinology and Metabolism Research Institute, Shariati Hospital, Tehran University of Medical Sciences, 5th Floor, North Kargar Ave, 14114 Tehran, Iran e-mail: [email protected]; [email protected]
123
The index patient was born to non-related parents of Persian origin, presented with thyroid nodule at the age of 48 years (Fig. 1). His past medical history was unremarkable. He had no history of hypertensive crisis or headache. On physical examination, height and body mass index recorded as 180 cm and 18.1 kg/m2, respectively. He had marfanoid features including: dolichocephaly, skeletal deformations (pectus excavatum), arachnodactyly with positive thumb sign, decreased upper segment to lower segment (US/LS) ratio, and increased arm span-to-height ratio (More than [1.05). Fine needle aspiration biopsy was compatible with MTC and preoperational screening for pheochromocytoma was in favor of bilateral adrenal mass. After obtaining informed consent, DNA was isolated from peripheral blood leukocytes using salting out method. Exones 10, 11, 13, 14, 15, and 16 of RET proto-oncogene localized to 10q 11.2 were examined by direct DNA sequencing [3]. This resulted in identification of mutations in Exon 11, codon 634, TGC [ CGC (Cystein [ Arginine), which was
Data Loading...
