PMID- 10634381
OWN - NLM
STAT- MEDLINE
DCOM- 20000203
LR  - 20230411
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 85
IP  - 1
DP  - 2000 Jan
TI  - Familial isolated hyperparathyroidism as a variant of multiple endocrine 
      neoplasia type 1 in a large Danish pedigree.
PG  - 165-7
AB  - We report here our genetic findings of a family in which 14 members were affected 
      with isolated primary hyperparathyroidism. Hyperparathyroidism is the main 
      feature of multiple endocrine neoplasia type 1 (MEN1), making the recently cloned 
      MEN1 gene a prime candidate gene in this family. Significantly positive lod 
      scores were achieved with D11S4946 (3.36) and D11S4940 (3.53), and by combining 
      the results from these two markers, a maximum positive lod score of 4.12 at 
      recombination fraction 0.00 was obtained. Mutation analysis of MEN1 performed by 
      full sequencing identified a missense mutation in exon 4, causing an amino acid 
      change from glutamine to proline at codon 260. This mutation (Q260P) was present 
      in all affected family members, and the inheritance of the mutation was in 
      complete agreement with the disease-associated haplotype. In comparison with the 
      recent functional studies of the menin protein interactions, this mutation is 
      located in a region with little or no binding activity to JunD and activating 
      protein-1 transcription factor. We conclude that some of the familial isolated 
      primary hyperparathyroidism families constitute a milder variant of MEN 1, which 
      is associated with a functionally milder missense mutation.
FAU - Kassem, M
AU  - Kassem M
AD  - University Department of Endocrinology and Metabolism, Aarhus Amtssyghus, 
      Denmark.
FAU - Kruse, T A
AU  - Kruse TA
FAU - Wong, F K
AU  - Wong FK
FAU - Larsson, C
AU  - Larsson C
FAU - Teh, B T
AU  - Teh BT
LA  - eng
PT  - Clinical Trial
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
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - DNA/genetics
MH  - Denmark
MH  - Exons/genetics
MH  - Female
MH  - Genetic Linkage/genetics
MH  - Genome, Human
MH  - Humans
MH  - Hyperparathyroidism/*genetics/metabolism
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/*genetics/metabolism
MH  - Mutation, Missense/genetics
MH  - Pedigree
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
EDAT- 2000/01/14 00:00
MHDA- 2000/01/14 00:01
CRDT- 2000/01/14 00:00
PHST- 2000/01/14 00:00 [pubmed]
PHST- 2000/01/14 00:01 [medline]
PHST- 2000/01/14 00:00 [entrez]
AID - 10.1210/jcem.85.1.6299 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2000 Jan;85(1):165-7. doi: 10.1210/jcem.85.1.6299.