Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene

J. D. Brensinger, S. J. Laken, M. C. Luce, S. M. Powell, Gail Vance, D. J. Ahnen, G. M. Petersen, S. R. Hamilton, F. M. Giardiello

Research output: Contribution to journalArticle

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Abstract

Background - Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. 'Attenuated' phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully. Aims - To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated. Results - Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer than one hundred colorectal adenomas) whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39 (14) years). Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted. Conclusions - Families with 3' mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5' mutations. Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.

Original languageEnglish (US)
Pages (from-to)548-552
Number of pages5
JournalGut
Volume43
Issue number4
StatePublished - 1998

Fingerprint

APC Genes
Adenomatous Polyposis Coli
Pedigree
Phenotype
Mutation
Codon
Lower Gastrointestinal Tract
Chromosomes, Human, Pair 5
Upper Gastrointestinal Tract
Germ-Line Mutation
Polyps
Adenoma
Colorectal Neoplasms
Genotype
Genes

Keywords

  • Adenomatous polyposis cob gene mutation
  • Attenuated adenomatous polyposis coli
  • Extracolonic lesions
  • Familial adenomatous polyposis

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Brensinger, J. D., Laken, S. J., Luce, M. C., Powell, S. M., Vance, G., Ahnen, D. J., ... Giardiello, F. M. (1998). Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. Gut, 43(4), 548-552.

Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. / Brensinger, J. D.; Laken, S. J.; Luce, M. C.; Powell, S. M.; Vance, Gail; Ahnen, D. J.; Petersen, G. M.; Hamilton, S. R.; Giardiello, F. M.

In: Gut, Vol. 43, No. 4, 1998, p. 548-552.

Research output: Contribution to journalArticle

Brensinger, JD, Laken, SJ, Luce, MC, Powell, SM, Vance, G, Ahnen, DJ, Petersen, GM, Hamilton, SR & Giardiello, FM 1998, 'Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene', Gut, vol. 43, no. 4, pp. 548-552.
Brensinger JD, Laken SJ, Luce MC, Powell SM, Vance G, Ahnen DJ et al. Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. Gut. 1998;43(4):548-552.
Brensinger, J. D. ; Laken, S. J. ; Luce, M. C. ; Powell, S. M. ; Vance, Gail ; Ahnen, D. J. ; Petersen, G. M. ; Hamilton, S. R. ; Giardiello, F. M. / Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene. In: Gut. 1998 ; Vol. 43, No. 4. pp. 548-552.
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abstract = "Background - Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. 'Attenuated' phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully. Aims - To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated. Results - Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer than one hundred colorectal adenomas) whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39 (14) years). Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted. Conclusions - Families with 3' mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5' mutations. Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.",
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T1 - Variable phenotype of familial adenomatous polyposis in pedigrees with 3' mutation in the APC gene

AU - Brensinger, J. D.

AU - Laken, S. J.

AU - Luce, M. C.

AU - Powell, S. M.

AU - Vance, Gail

AU - Ahnen, D. J.

AU - Petersen, G. M.

AU - Hamilton, S. R.

AU - Giardiello, F. M.

PY - 1998

Y1 - 1998

N2 - Background - Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. 'Attenuated' phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully. Aims - To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated. Results - Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer than one hundred colorectal adenomas) whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39 (14) years). Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted. Conclusions - Families with 3' mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5' mutations. Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.

AB - Background - Germline mutation in the adenomatous polyposis coli (APC) gene on chromosome 5 causes familial adenomatous polyposis. 'Attenuated' phenotype has been reported with mutation in the 5' end of the gene (5' to codon 158), but genotype-phenotype relations at the 3' end (3' to codon 1596) have not been described fully. Aims - To describe and compare colorectal and extracolonic phenotypes in a case series of families with mutation in the 3' end of the APC gene. Methods - Thirty one at risk or affected members from four families with a mutation in the APC gene located at codon 1979 or 2644 were evaluated. Results - Variable intrapedigree colorectal phenotype was observed: some members at older age had oligopolyposis (fewer than one hundred colorectal adenomas) whereas other members had classic polyposis at young age. Colorectal cancer was diagnosed at older mean age (50 (7) years) in the four families than in classic FAP pedigrees (39 (14) years). Extracolonic lesions characteristic of FAP occurred with 3' APC mutations, but variability in intrapedigree and interpedigree extracolonic phenotype and dissociation of severity of extracolonic manifestations from number of colorectal polyps was noted. Conclusions - Families with 3' mutations of the APC gene exhibit variable intrapedigree phenotype similar to the heterogeneity noted in families with proximal 5' mutations. Genotyping of FAP and oligopolyposis pedigrees can guide appropriate surveillance of the upper and lower gastrointestinal tract in affected members.

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