Linkage Analyses of Multiple Endocrine Neoplasia, Type 2A (MEN-2A) with 20 DNA Polymorphisms: 5% of the Genome Excluded

1986 ◽  
Vol 36 (4) ◽  
pp. 243-249 ◽  
Author(s):  
K.K. Kidd ◽  
J.R. Kidd ◽  
C.M. Castiglione ◽  
M. Genel ◽  
J. Darby ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Dna Polymorphisms ◽  
Linkage Analyses ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

scholarly journals Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634)

2014 ◽  
Vol 142 (1-2) ◽  
pp. 72-74 ◽  
Author(s):  
Maja Jesic ◽  
Milina Tancic-Gajic ◽  
Milos Jesic ◽  
Vladan Zivaljevic ◽  
Silvija Sajic ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Prophylactic Thyroidectomy ◽  
Urinary Catecholamines ◽  
Serum Calcitonin ◽  
Long Term Outcome ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A

Introduction. The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. Case Outline. This is a case report of 3-year-old boy from the MEN 2A family (the boy?s father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is <2 pg/ml (normal <13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Conclusion. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

scholarly journals A Novel Case of Multiple Endocrine Neoplasia Type 2A Associated with Two de Novo Mutations of the RETProtooncogene*

1999 ◽  
Vol 84 (10) ◽  
pp. 3522-3527 ◽  
Author(s):  
Alessandra Tessitore ◽  
Antonio A. Sinisi ◽  
Daniela Pasquali ◽  
Monica Cardone ◽  
Domenico Vitale ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
De Novo ◽  
Multiple Endocrine Neoplasia Type ◽  
Pcr Analysis ◽  
De Novo Mutations ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
A Cell ◽  
Glycine Substitution ◽  
Men 2A

Abstract We report a novel case of multiple endocrine neoplasia type 2A (MEN 2A) associated with two mutations of the protooncogene RET. One affects codon 634 and causes a cysteine to arginine substitution; the second at codon 640 causes an alanine to glycine substitution in the transmembrane region. The two mutations were present on the same RET allele and were detected in germline and tumor DNA. Both mutations were de novo, i.e. they were not found in the DNA of the parents or relatives. Immunohistochemical and RT-PCR analysis showed that the pheochromocytoma expressed calcitonin as well as both RET alleles. A cell line established from the tumor and propagated in culture sustained the expression of RET and calcitonin, as did the original pheochromocytoma. Because the patient presented with medullary thyroid carcinoma and pheochromocytoma without parathyroid gland involvement, we speculate that this clinical picture could be correlated with the two RET mutations and to the unusual calcitonin production. This is the first report of a MEN 2A case due to two mutations of the RET gene and associated with a calcitonin-producing pheochromocytoma.

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

Prophylactic thyroidectomy in multiple endocrine neoplasia type 2A in children: a single centre experience

2019 ◽  
Vol 32 (8) ◽  
pp. 889-893
Author(s):  
Cristina Garcés Visier ◽  
Manuel Espinoza Vega ◽  
Pilar Guillén Redondo ◽  
Juan Carlos Ollero Fresno ◽  
Henar Souto Romero ◽  
...  
Keyword(s):  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Long Term Results ◽  
Prophylactic Thyroidectomy ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Cervical Lymphadenectomy ◽  
Men 2A

Abstract Background To describe the complications and long-term results in patients with multiple endocrine neoplasia type 2A (MEN 2A) syndrome in whom a prophylactic thyroidectomy was performed, in relation to the recommendations of the American Thyroid Association (ATA). Methods A retrospective study of 14 patients with MEN 2A thyroidectomized between 2000 and 2017. We reviewed demographic, clinical, analytical and radiological data. Postoperative complications and long-term follow-up were analyzed. Results We treated eight boys and six girls with a median age of 5 years old (range 2–10). The predominant genetic mutation belonged to codon 634 (8/14, 57.14%). Total thyroidectomy (TT) without cervical lymphadenectomy was performed in all patients. A right upper parathyroidectomy was performed in one patient due to intraoperative suspicion of increased volume. Histological study revealed no alterations. Two patients presented transient hypocalcemia postoperatively and no patient had permanent hypocalcemia or nerve damage. Pathological anatomy confirmed medullary thyroid microcarcinoma in 5/14 patients: all carrying codon 634 mutation and three of them with preoperative basal calcitonin levels <20 pg/mL. No recurrences or metastases have been detected after a mean follow-up of 8 years. A patient with codon 634 mutation developed a unilateral pheochromocytoma at 25 years of age. No patient has presented hyperparathyroidism. Conclusions Prophylactic thyroidectomy without cervical lymphadenectomy is an effective and safe preventive treatment in patients with MEN 2A syndrome when it is performed by experienced surgeons in reference centers.

scholarly journals Primary hyperparathyroidism as first manifestation in multiple endocrine neoplasia type 2A: an international multicenter study

2020 ◽  
Vol 9 (6) ◽  
pp. 489-497 ◽  
Author(s):  
Louise Vølund Larsen ◽  
Delphine Mirebeau-Prunier ◽  
Tsuneo Imai ◽  
Cristina Alvarez-Escola ◽  
Kornelia Hasse-Lazar ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Multicenter Study ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Parathyroid Surgery ◽  
Node Positive ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Index Cases ◽  
Men 2A

Objective Multiple endocrine neoplasia type 2A (MEN 2A) is a rare syndrome caused by RET germline mutations and has been associated with primary hyperparathyroidism (PHPT) in up to 30% of cases. Recommendations on RET screening in patients with apparently sporadic PHPT are unclear. We aimed to estimate the prevalence of cases presenting with PHPT as first manifestation among MEN 2A index cases and to characterize the former cases. Design and methods An international retrospective multicenter study of 1085 MEN 2A index cases. Experts from MEN 2 centers all over the world were invited to participate. A total of 19 centers in 17 different countries provided registry data of index cases followed from 1974 to 2017. Results Ten cases presented with PHPT as their first manifestation of MEN 2A, yielding a prevalence of 0.9% (95% CI: 0.4–1.6). 9/10 cases were diagnosed with medullary thyroid carcinoma (MTC) in relation to parathyroid surgery and 1/10 was diagnosed 15 years after parathyroid surgery. 7/9 cases with full TNM data were node-positive at MTC diagnosis. Conclusions Our data suggest that the prevalence of MEN 2A index cases that present with PHPT as their first manifestation is very low. The majority of index cases presenting with PHPT as first manifestation have synchronous MTC and are often node-positive. Thus, our observations suggest that not performing RET mutation analysis in patients with apparently sporadic PHPT would result in an extremely low false-negative rate, if no other MEN 2A component, specifically MTC, are found during work-up or resection of PHPT.

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.

scholarly journals A Family of Multiple Endocrine Neoplasia Type 2A (MEN 2A) with Cys630Tyr RET Germline Mutation: Report of a Case

2007 ◽  
Vol 54 (4) ◽  
pp. 531-535 ◽  
Author(s):  
Hiroyuki YONEKAWA ◽  
Iwao SUGITANI ◽  
Yoshihide FUJIMOTO ◽  
Masami ARAI ◽  
Noriko YAMAMOTO
Keyword(s):  
Germline Mutation ◽  
Multiple Endocrine Neoplasia ◽  
Multiple Endocrine Neoplasia Type ◽  
Endocrine Neoplasia ◽  
Endocrine Neoplasia Type ◽  
Men 2A
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