Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1)

Burgess, John; Nord, Brita; David, Ruben; Greenaway, TM; Parameswaran, V.; Larsson, Catharina; Shepherd, J. J.; Teh, Bin Tean

doi:10.1046/j.1365-2265.2000.01032.x

Cited by 85 publications

(76 citation statements)

References 21 publications

(19 reference statements)

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“…Such rare cases are called MEN1 phenocopies and do not need further surveillance for MEN1. 44,48,49 In the other hand, genetic testing for MEN1 mutations might disclose inherited cases within "sporadic" patients presenting either HPT at early ages (< 30 yr) or recurrent HPT. The latter patients should be genetically tested, and if a germline mutation is detected, a total parathyroidectomy followed by an autograph to the forearm or subtotal parathyroidectomy should be performed, instead of adenomectomy.…”

Section: Discussionmentioning

confidence: 99%

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

Lourenço-Jr

Toledo

Coutinho

et al. 2007

Clinics

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METHODS:The clinical diagnosis of MEN1 was made in accordance with the Consensus on multiple endocrine neoplasias. Mutation analysis of the entire MEN1 tumor suppressor gene and genetic screening of at-risk family members were performed by direct sequencing. To analyze the implementation of genetic diagnosis, the studied patients were separated into 3 groups: MEN1 index cases (group I), clinically diagnosed MEN1 cases (group II), and genetically diagnosed MEN1 cases (group III). RESULTS: In total, 154 individuals were clinically and genetically studied. We identified 12 different MEN1 mutations. Fifty-two MEN1 cases were identified: 13 in group I, 28 in group II, and 11 in group III. The mean age in group III (27.0 years) was significantly lower than in groups I (39.5 years) and II (42.4 years; P = 0.03 and P = 0.01, respectively). Patients in groups I and II mostly presented 2 or 3 MEN1-related tumors, while 81.8% of those in group III presented 1 or no MEN1-related tumor. Additionally, in group III, 45.4% of cases were asymptomatic, and no metastasis or death was verified. Surveillance for MEN1 mutations allowed the exclusion of 102 noncarriers, including a case of MEN1 phenocopy. CONCLUSION: Our data supports the benefits of clinical and genetic screening for multiple endocrine neoplasia type 1 in the management of this syndrome.

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Section: Discussionmentioning

confidence: 99%

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

Lourenço-Jr

Toledo

Coutinho

et al. 2007

Clinics

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“…Thirty-four patients were clinically identified (cases 1-34). Of them, 30 (88.2%) were also genetically documented as 308delC MEN1 mutation carriers (cases 1-30), and 28 could be fully examined clinically (cases 1-28) and were followed for a period of 6 months up to 10 years; the phenotype in two other patients was only partially documented (cases [29][30]. In the four cases without genetic analysis (cases 31-34), a strong clinical history of MEN1-related tumors was reported.…”

Section: Genealogical and Geographic Analysismentioning

confidence: 99%

“…Notably, all five previously reported very large MEN1 genealogies were associated with founder chromosomes (12,13,25,26). Founder effects were documented in these five very large families by combining genetic studies (same germline MEN1 mutation and common haplotype) and clinical investigations with genealogical data associated with a common geographic origin (12)(13)(14)(25)(26)(27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 99%

Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile

Lourenço¹,

Toledo²,

Mackowiak³

et al. 2008

European Journal of Endocrinology

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Objective: Only few large families with multiple endocrine neoplasia type 1 (MEN1) have been documented. Here, we aimed to investigate the clinical features of a seven-generation Brazilian pedigree, which included 715 at-risk family members. Design: Genealogical and geographic analysis was used to identify the MEN1 pedigree. Clinical and genetic approach was applied to characterize the phenotypic and genotypic features of the family members. Results: Our genetic data indicated that a founding mutation in the MEN1 gene has occurred in this extended Brazilian family. Fifty family members were diagnosed with MEN1. Very high frequencies of functioning and non-functioning MEN1-related tumors were documented and the prevalence of prolactinoma (29.6%) was similar to that previously described in prolactinoma-variant Burin (32%). In addition, bone mineral density analysis revealed severe osteoporosis (T, K2.87G0.32) of compact bone (distal radius) in hyperparathyroidism (HPT)/MEN1 patients, while marked bone mineral loss in the lumbar spine (T, K1.95G0.39), with most cancellous bone, and femoral neck (mixed composition; T, K1.48G0.27) were also present. Conclusions: In this study, we described clinically and genetically the fifth largest MEN1 family in the literature. Our data confirm previous findings suggesting that prevalence of MEN1-related tumors in large families may differ from reports combining cumulative data of small families. Furthermore, we were able to evaluate the bone status in HPT/MEN1 cases, a subject that has been incompletely approached in the literature. We discussed the bone loss pattern found in our MEN1 patients comparing with that of patients with sporadic primary HPT.European Journal of Endocrinology 159 259-274

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“…2 is an inherited syndrome, with development of neoplasia in several endocrine organs including pancreatic islets (1)(2)(3)(4). The gene mutated in this syndrome, MEN1, encodes a nuclear protein of 610 amino acids, menin (5,6).…”

Section: Multiple Endocrine Neoplasia Type I (Men1)mentioning

confidence: 99%

Menin Is Required for Optimal Processing of the MicroRNA let-7a

Gurung

Muhammad

Hua

2014

Journal of Biological Chemistry

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Background: Menin represses pancreatic beta cell proliferation. Results: Menin promotes processing of let-7a, whose target IRS2 plays an important role in insulin signaling and beta cell proliferation. Conclusion: Menin represses beta cell proliferation partly via regulation of miRNA biogenesis. Significance: Understanding how menin represses beta cell proliferation will aid toward improving therapies targeting endocrine tumors and metabolic diseases including diabetes.

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Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1)

Cited by 85 publications

References 21 publications

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

The Impact of Clinical and Genetic Screenings on the Management of the Multiple Endocrine Neoplasia Type 1

Multiple endocrine neoplasia type 1 in Brazil: MEN1 founding mutation, clinical features, and bone mineral density profile

Menin Is Required for Optimal Processing of the MicroRNA let-7a

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