PMID- 9671267
OWN - NLM
STAT- MEDLINE
DCOM- 19980917
LR  - 20220408
IS  - 1059-7794 (Print)
IS  - 1059-7794 (Linking)
VI  - 12
IP  - 2
DP  - 1998
TI  - Analysis of recurrent germline mutations in the MEN1 gene encountered in 
      apparently unrelated families.
PG  - 75-82
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder that 
      manifests as varying combinations of tumors of endocrine and other tissues 
      (parathyroids, pancreatic islets, duodenal endocrine cells, the anterior 
      pituitary and others). The MEN1 gene is on chromosome 11q13; it was recently 
      identified by positional cloning. We previously reported 32 different germline 
      mutations in 47 of the 50 familial MEN1 probands studied at the NIH. Eight 
      different germline MEN1 mutations were encountered repeatedly in two or more 
      apparently unrelated families. We analyzed the haplotypes of families with 
      recurrent MEN1 mutations with seven polymorphic markers in the 11q13 region 
      surrounding the MEN1 gene (from D11S1883 to D11S4908). Disease haplotypes were 
      inferred from germline DNA and also from tumors with 11ql3 loss of 
      heterozygosity. Two different disease haplotype cores were shared by apparently 
      unrelated families for two mutations in exon 2 (five families with 416delC and 
      six families with 512delC). These two repeat mutations were associated with the 
      two founder effects that we reported in a prior haplotype analysis. The disease 
      haplotypes for each of the other six repeat mutations (seen twice each) were 
      discordant, suggesting independent origins of these recurrent mutations. Most of 
      the MEN1 germline mutations including all of those recurring independently occur 
      in regions of CpG/CpNpG, short DNA repeats or single nucleotide repeat motifs. In 
      conclusion, recurring germline mutations account for about half of the mutations 
      in North American MEN1 families. They result from either founder effects or 
      independent occurrence of one mutation more than one time.
FAU - Agarwal, S K
AU  - Agarwal SK
AD  - National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, 
      Maryland 20892, USA.
FAU - Debelenko, L V
AU  - Debelenko LV
FAU - Kester, M B
AU  - Kester MB
FAU - Guru, S C
AU  - Guru SC
FAU - Manickam, P
AU  - Manickam P
FAU - Olufemi, S E
AU  - Olufemi SE
FAU - Skarulis, M C
AU  - Skarulis MC
FAU - Heppner, C
AU  - Heppner C
FAU - Crabtree, J S
AU  - Crabtree JS
FAU - Lubensky, I A
AU  - Lubensky IA
FAU - Zhuang, Z
AU  - Zhuang Z
FAU - Kim, Y S
AU  - Kim YS
FAU - Chandrasekharappa, S C
AU  - Chandrasekharappa SC
FAU - Collins, F S
AU  - Collins FS
FAU - Liotta, L A
AU  - Liotta LA
FAU - Spiegel, A M
AU  - Spiegel AM
FAU - Burns, A L
AU  - Burns AL
FAU - Emmert-Buck, M R
AU  - Emmert-Buck MR
FAU - Marx, S J
AU  - Marx SJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Hum Mutat
JT  - Human mutation
JID - 9215429
RN  - 0 (Genetic Markers)
RN  - 0 (MEN1 protein, human)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - CpG Islands
MH  - DNA
MH  - Family Health
MH  - Female
MH  - Founder Effect
MH  - Genes, Tumor Suppressor
MH  - Genetic Markers
MH  - Germ-Line Mutation/*genetics
MH  - Haplotypes/genetics
MH  - Humans
MH  - Male
MH  - Multiple Endocrine Neoplasia Type 1/*genetics
MH  - Neoplasm Proteins/*genetics
MH  - Point Mutation
MH  - Polymorphism, Genetic
MH  - *Proto-Oncogene Proteins
MH  - Repetitive Sequences, Nucleic Acid
MH  - Sequence Analysis, DNA
EDAT- 1998/07/22 02:13
MHDA- 2000/06/22 10:00
CRDT- 1998/07/22 02:13
PHST- 1998/07/22 02:13 [pubmed]
PHST- 2000/06/22 10:00 [medline]
PHST- 1998/07/22 02:13 [entrez]
AID - 10.1002/(SICI)1098-1004(1998)12:2<75::AID-HUMU1>3.0.CO;2-T [pii]
AID - 10.1002/(SICI)1098-1004(1998)12:2<75::AID-HUMU1>3.0.CO;2-T [doi]
PST - ppublish
SO  - Hum Mutat. 1998;12(2):75-82. doi: 
      10.1002/(SICI)1098-1004(1998)12:2<75::AID-HUMU1>3.0.CO;2-T.