Tags

Type your tag names separated by a space and hit enter

Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families.
Hum Mutat. 1998; 12(2):75-82.HM

Abstract

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.

Authors+Show Affiliations

National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9671267

Citation

Agarwal, S K., et al. "Analysis of Recurrent Germline Mutations in the MEN1 Gene Encountered in Apparently Unrelated Families." Human Mutation, vol. 12, no. 2, 1998, pp. 75-82.
Agarwal SK, Debelenko LV, Kester MB, et al. Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. Hum Mutat. 1998;12(2):75-82.
Agarwal, S. K., Debelenko, L. V., Kester, M. B., Guru, S. C., Manickam, P., Olufemi, S. E., Skarulis, M. C., Heppner, C., Crabtree, J. S., Lubensky, I. A., Zhuang, Z., Kim, Y. S., Chandrasekharappa, S. C., Collins, F. S., Liotta, L. A., Spiegel, A. M., Burns, A. L., Emmert-Buck, M. R., & Marx, S. J. (1998). Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. Human Mutation, 12(2), 75-82.
Agarwal SK, et al. Analysis of Recurrent Germline Mutations in the MEN1 Gene Encountered in Apparently Unrelated Families. Hum Mutat. 1998;12(2):75-82. PubMed PMID: 9671267.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of recurrent germline mutations in the MEN1 gene encountered in apparently unrelated families. AU - Agarwal,S K, AU - Debelenko,L V, AU - Kester,M B, AU - Guru,S C, AU - Manickam,P, AU - Olufemi,S E, AU - Skarulis,M C, AU - Heppner,C, AU - Crabtree,J S, AU - Lubensky,I A, AU - Zhuang,Z, AU - Kim,Y S, AU - Chandrasekharappa,S C, AU - Collins,F S, AU - Liotta,L A, AU - Spiegel,A M, AU - Burns,A L, AU - Emmert-Buck,M R, AU - Marx,S J, PY - 1998/7/22/pubmed PY - 2000/6/22/medline PY - 1998/7/22/entrez SP - 75 EP - 82 JF - Human mutation JO - Hum Mutat VL - 12 IS - 2 N2 - 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. SN - 1059-7794 UR - https://www.unboundmedicine.com/medline/citation/9671267/Analysis_of_recurrent_germline_mutations_in_the_MEN1_gene_encountered_in_apparently_unrelated_families_ L2 - https://doi.org/10.1002/(SICI)1098-1004(1998)12:2<75::AID-HUMU1>3.0.CO;2-T DB - PRIME DP - Unbound Medicine ER -