PMID- 9329390
OWN - NLM
STAT- MEDLINE
DCOM- 19971117
LR  - 20101118
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 82
IP  - 10
DP  - 1997 Oct
TI  - A large multiple endocrine neoplasia type 1 family with clinical expression 
      suggestive of anticipation.
PG  - 3487-92
AB  - We describe a large multigenerational multiple endocrine neoplasia Type 1 (MEN1) 
      family with clinical expression suggestive of anticipation. In the second and 
      third generations, two deceased obligate gene carriers died at the ages of 85 and 
      76 without the history of MEN1, whereas two other living gene carriers above the 
      age of 65 have had no clinical evidence of MEN1 to date. In the fourth 
      generation, eight members were affected, with four having severe MEN1-related and 
      atypical malignancies: a case of metastatic endocrine pancreatic tumor, two cases 
      of metastatic thymic carcinoids, and a case of spinal ependymoma. In the fifth 
      generation, all five patients were below the age of 22 when the disease was 
      detected. MEN1 was confirmed in the family by linkage analysis using MEN1-linked 
      microsatellite markers and by identification of a nonsense mutation in the 
      MEN1/menin gene. Alleotyping showed loss of heterozygosity (LOH) involving the 
      wild-type alleles in seven tumors in the family including the ependymoma, which 
      is the first MEN1-related case that shows genetic abnormality in chromosome 
      11q13, suggesting that MEN1 gene might be involved in the tumorigenesis of a 
      subset of ependymomas. In relation to clinical anticipation, repeated expansion 
      studies were carried out but failed to detect any expansion. We conclude that 
      this is a unique MEN1 family and that an unknown genetic mechanism might be 
      contributing to the anticipation phenomenon. We demonstrate in this family that 
      all gene carriers, including the very young members, will need close and careful 
      follow-up.
FAU - Giraud, S
AU  - Giraud S
AD  - Department of Genetics, Edouard Herriot Hospital, Lyon, France.
FAU - Choplin, H
AU  - Choplin H
FAU - Teh, B T
AU  - Teh BT
FAU - Lespinasse, J
AU  - Lespinasse J
FAU - Jouvet, A
AU  - Jouvet A
FAU - Labat-Moleur, F
AU  - Labat-Moleur F
FAU - Lenoir, G
AU  - Lenoir G
FAU - Hamon, B
AU  - Hamon B
FAU - Hamon, P
AU  - Hamon P
FAU - Calender, A
AU  - Calender A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
SB  - IM
MH  - Adult
MH  - Age of Onset
MH  - Aged
MH  - Alleles
MH  - Cytogenetics
MH  - Disease Progression
MH  - Female
MH  - Genetic Linkage
MH  - Germ-Line Mutation
MH  - Heterozygote
MH  - Humans
MH  - Loss of Heterozygosity
MH  - Male
MH  - Middle Aged
MH  - Multiple Endocrine Neoplasia Type 1/epidemiology/*genetics/physiopathology
MH  - Pedigree
EDAT- 1997/11/05 00:00
MHDA- 1997/11/05 00:01
CRDT- 1997/11/05 00:00
PHST- 1997/11/05 00:00 [pubmed]
PHST- 1997/11/05 00:01 [medline]
PHST- 1997/11/05 00:00 [entrez]
AID - 10.1210/jcem.82.10.4052 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1997 Oct;82(10):3487-92. doi: 10.1210/jcem.82.10.4052.