PMID- 19953642
OWN - NLM
STAT- MEDLINE
DCOM- 20100312
LR  - 20091224
IS  - 1098-1004 (Electronic)
IS  - 1059-7794 (Linking)
VI  - 31
IP  - 1
DP  - 2010 Jan
TI  - Diagnostic challenges due to phenocopies: lessons from Multiple Endocrine 
      Neoplasia type1 (MEN1).
PG  - E1089-101
LID - 10.1002/humu.21170 [doi]
AB  - 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.
FAU - Turner, Jeremy J O
AU  - Turner JJ
AD  - Academic Endocrine Unit, Nuffield Department of Clinical Medicine, University of 
      Oxford, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill 
      Hospital, Oxford, OX3 7LJ, UK.
FAU - Christie, Paul T
AU  - Christie PT
FAU - Pearce, Simon H S
AU  - Pearce SH
FAU - Turnpenny, Peter D
AU  - Turnpenny PD
FAU - Thakker, Rajesh V
AU  - Thakker RV
LA  - eng
GR  - G9825289/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (CDC73 protein, human)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Calcium-Sensing)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Adult
MH  - Female
MH  - Humans
MH  - Hypercalcemia/diagnosis/genetics
MH  - Hyperparathyroidism/diagnosis/genetics
MH  - Male
MH  - Middle Aged
MH  - *Multiple Endocrine Neoplasia Type 1/diagnosis/genetics/physiopathology
MH  - Mutation
MH  - Pancreatic Neoplasms/diagnosis/genetics
MH  - Parathyroid Neoplasms/diagnosis/genetics
MH  - Phenotype
MH  - Proto-Oncogene Proteins/genetics
MH  - Receptors, Calcium-Sensing/genetics
MH  - Sequence Analysis, DNA
MH  - Tumor Suppressor Proteins/genetics
EDAT- 2009/12/03 06:00
MHDA- 2010/03/13 06:00
CRDT- 2009/12/03 06:00
PHST- 2009/12/03 06:00 [entrez]
PHST- 2009/12/03 06:00 [pubmed]
PHST- 2010/03/13 06:00 [medline]
AID - 10.1002/humu.21170 [doi]
PST - ppublish
SO  - Hum Mutat. 2010 Jan;31(1):E1089-101. doi: 10.1002/humu.21170.