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Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1).
Hum Mutat. 2010 Jan; 31(1):E1089-101.HM

Abstract

Phenocopies may confound the clinical diagnoses of hereditary disorders. We report phenocopies in Multiple Endocrine Neoplasia type 1 (MEN1), an autosomal dominant disorder, characterised by the combined occurrence of parathyroid, pituitary and pancreatic tumours. We studied 261 affected individuals from 74 families referred with a clinical diagnosis of MEN1 and sought inconsistencies between the mutational and clinical data. We identified four patients from unrelated families with phenocopies. Patients 1 and 2 from families with MEN1, developed prolactinomas as the sole endocrinopathy but they did not harbour the germline MEN1 mutation present in their affected relatives. Patient 3, had acromegaly and recurrent hypercalcaemia following parathyroidectomy, whilst patient 4 had parathyroid tumours and a microprolactinoma. Patients 3 and 4 and their relatives did not have MEN1 mutations, but instead had familial hypocalciuric hypercalcaemia (FHH) due to a calcium-sensing receptor mutation (p.Arg680Cys), and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome due to a hyperparathyroidism type 2 deletional-frameshift mutation (c.1239delA), respectively. Phenocopies may mimic MEN1 either by occurrence of a single sporadic endocrine tumour in a patient with familial MEN1, or occurrence of two endocrine abnormalities associated with different aetiologies. Phenocopies arose in >5% of MEN1 families, and awareness of them is important in the clinical management of MEN1 and other hereditary disorders.

Authors+Show Affiliations

Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Oxford, OX3 7LJ, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19953642

Citation

Turner, Jeremy J O., et al. "Diagnostic Challenges Due to Phenocopies: Lessons From Multiple Endocrine Neoplasia Type1 (MEN1)." Human Mutation, vol. 31, no. 1, 2010, pp. E1089-101.
Turner JJ, Christie PT, Pearce SH, et al. Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1). Hum Mutat. 2010;31(1):E1089-101.
Turner, J. J., Christie, P. T., Pearce, S. H., Turnpenny, P. D., & Thakker, R. V. (2010). Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1). Human Mutation, 31(1), E1089-101. https://doi.org/10.1002/humu.21170
Turner JJ, et al. Diagnostic Challenges Due to Phenocopies: Lessons From Multiple Endocrine Neoplasia Type1 (MEN1). Hum Mutat. 2010;31(1):E1089-101. PubMed PMID: 19953642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine Neoplasia type1 (MEN1). AU - Turner,Jeremy J O, AU - Christie,Paul T, AU - Pearce,Simon H S, AU - Turnpenny,Peter D, AU - Thakker,Rajesh V, PY - 2009/12/3/entrez PY - 2009/12/3/pubmed PY - 2010/3/13/medline SP - E1089 EP - 101 JF - Human mutation JO - Hum Mutat VL - 31 IS - 1 N2 - Phenocopies may confound the clinical diagnoses of hereditary disorders. We report phenocopies in Multiple Endocrine Neoplasia type 1 (MEN1), an autosomal dominant disorder, characterised by the combined occurrence of parathyroid, pituitary and pancreatic tumours. We studied 261 affected individuals from 74 families referred with a clinical diagnosis of MEN1 and sought inconsistencies between the mutational and clinical data. We identified four patients from unrelated families with phenocopies. Patients 1 and 2 from families with MEN1, developed prolactinomas as the sole endocrinopathy but they did not harbour the germline MEN1 mutation present in their affected relatives. Patient 3, had acromegaly and recurrent hypercalcaemia following parathyroidectomy, whilst patient 4 had parathyroid tumours and a microprolactinoma. Patients 3 and 4 and their relatives did not have MEN1 mutations, but instead had familial hypocalciuric hypercalcaemia (FHH) due to a calcium-sensing receptor mutation (p.Arg680Cys), and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome due to a hyperparathyroidism type 2 deletional-frameshift mutation (c.1239delA), respectively. Phenocopies may mimic MEN1 either by occurrence of a single sporadic endocrine tumour in a patient with familial MEN1, or occurrence of two endocrine abnormalities associated with different aetiologies. Phenocopies arose in >5% of MEN1 families, and awareness of them is important in the clinical management of MEN1 and other hereditary disorders. SN - 1098-1004 UR - https://www.unboundmedicine.com/medline/citation/19953642/Diagnostic_challenges_due_to_phenocopies:_lessons_from_Multiple_Endocrine_Neoplasia_type1__MEN1__ L2 - https://doi.org/10.1002/humu.21170 DB - PRIME DP - Unbound Medicine ER -