G2Cdb::Human Disease report

Disease id
D00000138
Name
Multiple endocrine neoplasia type I
Nervous system disease
no

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00001604 PLCB1
phospholipase C, beta 1 (phosphoinositide-specific)
Y (9003510) Microinsertion (MI) N
G00001604 PLCB1
phospholipase C, beta 1 (phosphoinositide-specific)
Y (9003510) Polymorphism (P) N
G00001604 PLCB1
phospholipase C, beta 1 (phosphoinositide-specific)
Y (9003511) Single nucleotide polymorphism (SNP) N
G00000031 HRAS
v-Ha-ras Harvey rat sarcoma viral oncogene homolog
Y (2565762) Deletion (D) Y

References

  • Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene.

    de Wit MJ, Landsvater RM, Sinke RJ, Geurts van Kessel A, Lips CJ and Höppener JW

    Department of Internal Medicine, University Hospital Utrecht, The Netherlands.

    Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by hyperplasia and neoplasia in several endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a 900-kb region on chromosome 11q13. The human phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene, which is located within this region, was considered to be a good candidate for the MEN 1 gene. In this study, the structure and expression of the PLC beta 3 gene in MEN 1 patients were investigated in more detail, to determine its potential role in MEN 1 tumorigenesis. Southern blot analysis, using blood and tumor DNA from affected persons from seven different MEN 1 families, did not reveal structural abnormalities in the PLC beta 3 gene. To detect possible point mutations, or other small structural aberrations, direct sequencing of PLC beta 3 cDNAs from two affected persons from two different MEN 1 families was performed, but no MEN 1-specific abnormalities were revealed. Several common nucleotide sequence polymorphisms were detected in these cDNAs, proving that both alleles of the PLC beta 3 gene were expressed and analyzed. In conclusion, these results exclude the PLC beta 3 gene as a candidate gene for MEN 1.

    Human genetics 1997;99;1;133-7

  • Exclusion of the phosphoinositide-specific phospholipase C beta 3 (PLCB3) gene as a candidate for multiple endocrine neoplasia type 1.

    Weber G, Grimmond S, Lagercrantz J, Friedman E, Phelan C, Carson E, Hayward N, Jacobovitz O, Nordenskjöld M and Larsson C

    Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.

    The predisposing genetic defect in multiple endocrine neoplasia type 1 has been assigned to chromosomal region 11q13. Our previous attempts to identify the MEN1 gene have resulted in the isolation of the phospholipase C beta 3 gene from the actual region. PLCB3 plays an important role in signal transduction and, moreover, shows loss of expression in some endocrine tumors, in accordance with a putative tumor suppressor gene function, and thus appears to be an excellent candidate for MEN1. We have therefore undertaken screening for constitutional mutations in individuals from MEN1 families. Several sequence alterations have been discovered, none of them however fulfilling the criteria for a disease-related mutation. We can now exclude PLCB3 from candidacy as the MEN1 gene.

    Human genetics 1997;99;1;130-2

  • Loss of the same alleles of HRAS1 and D11S151 in two independent pancreatic cancers from a patient with multiple endocrine neoplasia type 1.

    Yoshimoto K, Iizuka M, Iwahana H, Yamasaki R, Saito H, Saito S and Sekiya T

    Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.

    The DNAs from two independent pancreatic cancers (tumors 1 and 2) in a patient with multiple endocrine neoplasia type 1 were analyzed. No amplification or gross rearrangement of 19 protooncogenes was observed. However, Southern blot analysis using polymorphic DNA probes revealed loss of heterozygosity at loci on chromosome 11p in both tumors. In tumor 1, an extensive region including the HRAS1, PTH, CALCA, and D11S151 loci was deleted, while in tumor 2 loss of heterozygosity was limited at the HRAS1 and D11S151 loci. Because loss of heterozygosity at other chromosomal loci in the two tumors was quite rare, loss of genes on 11p might be nonrandom. It is noteworthy that the same allele at the HRAS1 locus and also the same allele at the D11S151 locus were lost in the two independent tumors. These results suggest that loss of genes at the HRAS1 and/or D11S151 loci plays an important role unmasking the remaining sequences probably having a recessive mutation.

    Cancer research 1989;49;10;2716-21

Literature (3)

Pubmed - human_disease

  • Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene.

    de Wit MJ, Landsvater RM, Sinke RJ, Geurts van Kessel A, Lips CJ and Höppener JW

    Department of Internal Medicine, University Hospital Utrecht, The Netherlands.

    Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by hyperplasia and neoplasia in several endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a 900-kb region on chromosome 11q13. The human phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene, which is located within this region, was considered to be a good candidate for the MEN 1 gene. In this study, the structure and expression of the PLC beta 3 gene in MEN 1 patients were investigated in more detail, to determine its potential role in MEN 1 tumorigenesis. Southern blot analysis, using blood and tumor DNA from affected persons from seven different MEN 1 families, did not reveal structural abnormalities in the PLC beta 3 gene. To detect possible point mutations, or other small structural aberrations, direct sequencing of PLC beta 3 cDNAs from two affected persons from two different MEN 1 families was performed, but no MEN 1-specific abnormalities were revealed. Several common nucleotide sequence polymorphisms were detected in these cDNAs, proving that both alleles of the PLC beta 3 gene were expressed and analyzed. In conclusion, these results exclude the PLC beta 3 gene as a candidate gene for MEN 1.

    Human genetics 1997;99;1;133-7

  • Exclusion of the phosphoinositide-specific phospholipase C beta 3 (PLCB3) gene as a candidate for multiple endocrine neoplasia type 1.

    Weber G, Grimmond S, Lagercrantz J, Friedman E, Phelan C, Carson E, Hayward N, Jacobovitz O, Nordenskjöld M and Larsson C

    Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden.

    The predisposing genetic defect in multiple endocrine neoplasia type 1 has been assigned to chromosomal region 11q13. Our previous attempts to identify the MEN1 gene have resulted in the isolation of the phospholipase C beta 3 gene from the actual region. PLCB3 plays an important role in signal transduction and, moreover, shows loss of expression in some endocrine tumors, in accordance with a putative tumor suppressor gene function, and thus appears to be an excellent candidate for MEN1. We have therefore undertaken screening for constitutional mutations in individuals from MEN1 families. Several sequence alterations have been discovered, none of them however fulfilling the criteria for a disease-related mutation. We can now exclude PLCB3 from candidacy as the MEN1 gene.

    Human genetics 1997;99;1;130-2

  • Loss of the same alleles of HRAS1 and D11S151 in two independent pancreatic cancers from a patient with multiple endocrine neoplasia type 1.

    Yoshimoto K, Iizuka M, Iwahana H, Yamasaki R, Saito H, Saito S and Sekiya T

    Oncogene Division, National Cancer Center Research Institute, Tokyo, Japan.

    The DNAs from two independent pancreatic cancers (tumors 1 and 2) in a patient with multiple endocrine neoplasia type 1 were analyzed. No amplification or gross rearrangement of 19 protooncogenes was observed. However, Southern blot analysis using polymorphic DNA probes revealed loss of heterozygosity at loci on chromosome 11p in both tumors. In tumor 1, an extensive region including the HRAS1, PTH, CALCA, and D11S151 loci was deleted, while in tumor 2 loss of heterozygosity was limited at the HRAS1 and D11S151 loci. Because loss of heterozygosity at other chromosomal loci in the two tumors was quite rare, loss of genes on 11p might be nonrandom. It is noteworthy that the same allele at the HRAS1 locus and also the same allele at the D11S151 locus were lost in the two independent tumors. These results suggest that loss of genes at the HRAS1 and/or D11S151 loci plays an important role unmasking the remaining sequences probably having a recessive mutation.

    Cancer research 1989;49;10;2716-21

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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