Utility of RET Mutation Analysis in Multiple Endocrine Neoplasia Type 2

1999 ◽  
Vol 123 (11) ◽  
pp. 1047-1049 ◽  
Author(s):  
Walter W. Noll
Keyword(s):  
Mutation Analysis ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Specific Test ◽  
Ret Mutation ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
The Individual

Abstract Objective.—To review the role of RET mutation analysis in the diagnosis of multiple endocrine neoplasia type 2 (MEN 2) and in presymptomatic screening for this disorder. Data Sources.—Review of the medical literature and current clinical practice. Conclusions.—RET mutation analysis is a sensitive and specific test for MEN 2. It plays a pivotal role in the diagnosis and management of patients and families with MEN 2 and in the individual who presents with an apparently sporadic medullary thyroid carcinoma or pheochromocytoma. These disorders may first come to the attention of either the anatomic or clinical pathologist, who has the opportunity to see that appropriate testing is done. As with any familial disease, professional genetic counseling is an important part of the care of these patients.

scholarly journals Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes

2010 ◽  
Vol 163 (6) ◽  
pp. 963 ◽  
Author(s):  
Cristina Romei ◽  
Stefano Mariotti ◽  
Laura Fugazzola ◽  
Augusto Taccaliti ◽  
Furio Pacini ◽  
...  
Keyword(s):  
Network Analysis ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Related Article ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Article Type

The journal and the authors apologise for an error in the name of one of the authors (appears as Verga Uberta) of this article published in the European Journal of Endocrinology Vol 163 301–308. The correct name of the author should be Uberta Verga and not as published.

Linkage Analyses of Multiple Endocrine Neoplasia, Type 2 (MEN-2) with 23 Classical Genetic Polymorphisms

1986 ◽  
Vol 36 (1) ◽  
pp. 6-11 ◽  
Author(s):  
Susan D. Kruger ◽  
Joseph M. Gertner ◽  
Robert S. Sparkes ◽  
Lori E. Haedt ◽  
Michol Crist ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Classical Genetic ◽  
Linkage Analyses ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2—relevance of specific mutations in the RET proto-oncogene

1996 ◽  
Vol 135 (2) ◽  
pp. 222-225 ◽  
Author(s):  
Karin Frank-Raue ◽  
Thomas Kratt ◽  
Wolfgang Höppner ◽  
Heinz Buhr ◽  
Reinhard Ziegler ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Mutational Analysis ◽  
Multiple Endocrine Neoplasia Type ◽  
Diagnosis And Management ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Highly Sensitive ◽  
Sporadic Cases

Frank-Raue K, Kratt T, Höppner W, Buhr H, Ziegler R, Raue F. Diagnosis and management of pheochromocytomas in patients with multiple endocrine neoplasia type 2—relevance of specific mutations in the RET proto-oncogene. Eur J Endocrinol 1996;135:222–5. ISSN 0804–4643 It has been suggested that specific mutations in the RET proto-oncogene correlate with clinical manifestation of the multiple endocrine neoplasia type 2 (MEN 2) syndrome. We retrospectively analyzed 61 patients with MEN 2, 28 with associated pheochromocytoma, regarding the relevance of specific mutations in the RET proto-oncogene and the diagnostic sensitivity of catecholamine screening and localization procedures. The present study shows that the position of the RET mutation is related to disease phenotype; codon 634 mutations are predictive of families predisposed to pheochromocytoma. In 18% of our patients, the diagnosis of pheochromocytoma preceded detection of medullary thyroid carcinoma. Therefore, mutation analysis of the RET gene should be performed in apparently "sporadic" cases of pheochromocytoma to confirm or exclude MEN 2. The most sensitive biochemical marker for pheochromocytoma in MEN 2 is 24-h urinary epinephrine excretion. Computed tomography, magnetic resonance imaging and MIBG scintigraphy are all highly sensitive methods to localize pheochromocytoma. We conclude that, in all families with MEN 2, mutational analysis of the RET proto-oncogene should be performed, both to identify gene carriers for MEN 2 and to identify specific mutations that are more strongly associated with pheochromocytoma. Karin Frank-Raue, Department of Internal Medicine, Endocrinology & Metabolism, Bergheimer Straße 58, 69115 Heidelberg, Germany

Multiple endocrine neoplasia type 2

2011 ◽  
pp. 951-953
Author(s):  
Niamh M. Martin ◽  
Karim Meeran ◽  
Stephen R. Bloom
Keyword(s):  
Thyroid Carcinoma ◽  
Medullary Thyroid Carcinoma ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Medullary Thyroid ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Multiple endocrine neoplasia type 2 (MEN 2) is a rare cancer susceptibility syndrome which has at least three distinct variants: MEN 2A, MEN 2B, and familial medullary thyroid carcinoma (FMTC). The syndrome was first described by John Sipple in 1961 (1). The features of MEN 2A and its clinical variants are outlined in Box 6.12.1. Medullary thyroid carcinoma (MTC) is seen in all variants of MEN 2A and is frequently the earliest neoplastic manifestation, reflecting its earlier and overall higher penetrance. MEN 2 is due to the autosomal dominant inheritance of a germline missense mutation in the ‘hot-spot’ regions of the rearranged during transfection (RET) (OMIM 164761) proto-oncogene (2, 3). MEN 2 has an estimated prevalence of 1:30 000, with MEN 2A accounting for more than 75% of cases. The introduction of RET screening in family members of affected individuals has significantly altered the clinical outcome of MEN 2, by allowing prophylactic surgery for MTC, and screening enabling early intervention for phaeochromocytoma (4, 5). Prior to the availability of genetic screening, more that half of MEN 2 affected individuals died before or during the fifth decade from metastatic MTC or cardiovascular complications from an underlying phaeochromocytoma.

Multiple endocrine neoplasia type 1

2011 ◽  
pp. 945-950
Author(s):  
R.V. Thakker
Keyword(s):  
Family History ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Glands ◽  
Men 1 ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type

Multiple endocrine neoplasia (1, 2) is characterized by the occurrence of tumours involving two or more endocrine glands within a single patient. The disorder has previously been referred to as multiple endocrine adenopathy (MEA) or the pluriglandular syndrome. However, glandular hyperplasia and malignancy may also occur in some patients and the term multiple endocrine neoplasia (MEN) is now preferred. There are two major forms of multiple endocrine neoplasia, referred to as type 1 and type 2, and each form is characterized by the development of tumours within specific endocrine glands (Table 6.11.1). Thus, the combined occurrence of tumours of the parathyroid glands, the pancreatic islet cells, and the anterior pituitary is characteristic of multiple endocrine neoplasia type 1 (MEN 1), which is also referred to as Wermer’s syndrome. However, in multiple endocrine neoplasia type 2 (MEN 2), which is also called Sipple’s syndrome, medullary thyroid carcinoma (MTC) occurs in association with phaeochromocytoma, and three clinical variants, referred to as MEN 2a, MEN 2b and MTC-only, are recognized (Table 6.11.1). Although MEN 1 and MEN 2 usually occur as distinct and separate syndromes as outlined above, some patients occasionally may develop tumours that are associated with both MEN 1 and MEN 2. For example, patients suffering from islet cell tumours of the pancreas and phaeochromocytomas or from acromegaly and phaeochromocytoma have been described, and these patients may represent ‘overlap’ syndromes. All these forms of MEN may either be inherited as autosomal dominant syndromes or they may occur sporadically, i.e. without a family history. However, this distinction between sporadic and familial cases may sometimes be difficult as in some sporadic cases the family history may be absent because the parent with the disease may have died before developing symptoms. In this chapter, the main clinical features and molecular genetics of the MEN 1 syndrome will be discussed.

scholarly journals Denaturing gradient gel electrophoresis to diagnose multiple endocrine neoplasia type 2

1996 ◽  
Vol 42 (4) ◽  
pp. 598-603 ◽  
Author(s):  
R D Blank ◽  
C A Sklar ◽  
M L Martin
Keyword(s):  
Gel Electrophoresis ◽  
Multiple Endocrine Neoplasia ◽  
Denaturing Gradient Gel Electrophoresis ◽  
Multiple Endocrine Neoplasia Type ◽  
Men 2 ◽  
Endocrine Neoplasia ◽  
Pathogenic Mutations ◽  
Endocrine Neoplasia Type ◽  
Gradient Gel Electrophoresis

Abstract Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant cancer syndrome caused by mutations in the RET protooncogene. Others have already demonstrated the value of genetic testing in known MEN 2 kindreds. Previously described approaches to DNA-level diagnosis, particularly of index cases, are tedious. We developed appropriate denaturing gradient gel electrophoresis (DGGE) conditions for analysis of exons 10, 11, and 16 of this gene, where many of the pathogenic mutations map. We screened 16 members of a three-generation MEN 2 kindred by DGGE and found five affected but still asymptomatic patients, ranging in age from 5 to 67 years. We used DGGE to localize the pathogenic mutations and screen at-risk individuals in several other kindreds. DGGE--which requires no radioactive, fluorescent, or chemiluminescent labeling--is ideally suited to the diagnosis of MEN 2 because of the syndrome's dominant genetics and the rarity of clinically silent variants in the RET gene.

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