PMID- 10931102
OWN - NLM
STAT- MEDLINE
DCOM- 20001010
LR  - 20230411
IS  - 0300-0664 (Print)
IS  - 0300-0664 (Linking)
VI  - 53
IP  - 2
DP  - 2000 Aug
TI  - Phenotype and phenocopy: the relationship between genotype and clinical phenotype 
      in a single large family with multiple endocrine neoplasia type 1 (MEN 1).
PG  - 205-11
AB  - 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 1 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 
      nonspecific, 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.
FAU - Burgess, J R
AU  - Burgess JR
AD  - Departments of Diabetes and Endocrine Services; Clinical Chemistry, Royal Hobart 
      Hospital, Hobart, Australia. jburges@postoffice.utas.edu.au
FAU - Nord, B
AU  - Nord B
FAU - David, R
AU  - David R
FAU - Greenaway, T M
AU  - Greenaway TM
FAU - Parameswaran, V
AU  - Parameswaran V
FAU - Larsson, C
AU  - Larsson C
FAU - Shepherd, J J
AU  - Shepherd JJ
FAU - Teh, B T
AU  - Teh BT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Endocrinol (Oxf)
JT  - Clinical endocrinology
JID - 0346653
RN  - 0 (Genetic Markers)
SB  - IM
MH  - Adult
MH  - Case-Control Studies
MH  - Chi-Square Distribution
MH  - Female
MH  - Genetic Markers
MH  - Genotype
MH  - Haplotypes
MH  - Heterozygote
MH  - Humans
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/diagnosis/*genetics
MH  - Pedigree
MH  - Phenotype
MH  - Polymorphism, Single-Stranded Conformational
MH  - Sequence Analysis, DNA
EDAT- 2000/08/10 11:00
MHDA- 2000/10/14 11:01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2000/10/14 11:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
AID - cen1032 [pii]
AID - 10.1046/j.1365-2265.2000.01032.x [doi]
PST - ppublish
SO  - Clin Endocrinol (Oxf). 2000 Aug;53(2):205-11. doi: 
      10.1046/j.1365-2265.2000.01032.x.