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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)


Burgess, JR and Nord, B and David, R and Greenaway, TM and Parameswaran, V and Larsson, C and Shepherd, JJ and Teh, BT, Phenotype and phenocopy: the relationship between genotype and clinical phenotype in a single large family with multiple endocrine neoplasia type 1 (MEN 1), Clinical Endocrinology, 53 pp. 205-211. ISSN 0300-0664 (2000) [Refereed Article]

DOI: doi:10.1046/j.1365-2265.2000.01032.x


BACKGROUND: The majority of reports describing the natural history and prognosis of multiple endocrine neoplasia type 1 (MEN 1) utilize phenotypic rather than molecular genetic criteria to establish a diagnosis of MEN 1. OBJECTIVES AND PATIENTS: We sought to determine the spectrum of endocrine abnormality amongst 152 members (64 gene carriers and 88 noncarriers) of a large MEN 1 family in whom a determination of MEN 1 status had previously been made by phenotype screening. The predictive utility of both clinical and molecular screening techniques are described. RESULTS: A novel IVS2-3 (C-G) MEN1 mutation was identified in affected members of this family. Seven (10%) of 71 individuals satisfying clinical diagnostic criteria for MEN 1 were found to be genetically negative (excluded by mutation analysis and haplotyping) for MEN 1. These cases of MEN I phenocopy comprised four cases of primary hyperparathyroidism, two 'nonsecretory' pituitary adenoma and one case of coincident prolactinoma and hyperparathyroidism. Three of the patients with hyperparathyroidism had previously required parathyroidectomy and each had achieved normocalcaemia following parathyroid resection. Predictive genetic testing prospectively identified three children with the MEN 1 genotype. Serum calcium was normal at the time of their initial molecular genetic diagnosis. In each case hyperparathyroidism subsequently developed during adolescence. CONCLUSION: Multiple endocrine neoplasia type 1 phenocopy is an important differential diagnosis in patients exhibiting an multiple endocrine neoplasia type 1 phenotype. This is a relevant consideration, particularly when the diagnosis of multiple endocrine neoplasia type 1 is made using sensitive, but non-specific, criteria such as mild hyperparathyroidism, pituitary micoadenoma, and hyperprolactinaemia. Confirmatory genetic testing should be undertaken to confirm clinical diagnoses of multiple endocrine neoplasia type 1.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Oncology and carcinogenesis
Research Field:Oncology and carcinogenesis not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Burgess, JR (Professor John Burgess)
UTAS Author:Greenaway, TM (Dr Tim Greenaway)
UTAS Author:Shepherd, JJ (Professor Joseph Shepherd)
ID Code:19509
Year Published:2000
Web of Science® Times Cited:71
Deposited By:Medicine
Deposited On:2000-08-01
Last Modified:2001-05-03

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