Mutational analysis of patients with adenomatous polyposis: identical inactivating mutations in unrelated individuals.

Samples of constitutional DNA from 60 unrelated patients with adenomatous polyposis coli (APC) were examined for mutations in the APC gene. Five inactivating mutations were observed among 12 individuals with APC; all were different from the six inactivating mutations previously reported in this panel of patients. The newly discovered mutations included single-nucleotide substitutions leading to stop codons and small deletions leading to frameshifts. Two of the mutations were observed in multiple APC families and in sporadic cases of APC; allele-specific PCR primers were designed for detecting mutations at these common sites. No missense mutations that segregated with the disease were found.

[1]  G. Thomas,et al.  Alleles of the APC gene: An attenuated form of familial polyposis , 1993, Cell.

[2]  M. Robertson,et al.  Identification of APC gene mutations in Italian adenomatous polyposis coli patients by PCR-SSCP analysis. , 1993, American journal of human genetics.

[3]  G. Thomas,et al.  Germ-line mutations in the first 14 exons of the adenomatous polyposis coli (APC) gene. , 1993, American journal of human genetics.

[4]  R. Fodde,et al.  Eight novel inactivating germ line mutations at the APC gene identified by denaturing gradient gel electrophoresis. , 1992, Genomics.

[5]  K. Kinzler,et al.  Corrections and Clarifications: Multiple Intestinal Neoplasia Caused By a Mutation in the Murine Homolog of the APC Gene , 1992, Science.

[6]  K. Kinzler,et al.  Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[7]  J. Gordon,et al.  The Min (multiple intestinal neoplasia) mutation: its effect on gut epithelial cell differentiation and interaction with a modifier system , 1992, The Journal of cell biology.

[8]  M. Leppert,et al.  A CA repeat 30-70 KB downstream from the adenomatous polyposis coli (APC) gene. , 1991, Nucleic acids research.

[9]  H. Bourne Suppression with a difference , 1991, Nature.

[10]  Margaret Robertson,et al.  Identification and characterization of the familial adenomatous polyposis coli gene , 1991, Cell.

[11]  S. Altschul,et al.  Identification of FAP locus genes from chromosome 5q21. , 1991, Science.

[12]  J. McPherson,et al.  Identification of deletion mutations and three new genes at the familial polyposis locus , 1991, Cell.

[13]  H Sugita,et al.  Exploring the molecular basis for variability among patients with Becker muscular dystrophy: dystrophin gene and protein studies. , 1991, American journal of human genetics.

[14]  H. Bourne Consider the coiled coil , 1991, Nature.

[15]  K. Kinzler,et al.  Identification of a gene located at chromosome 5q21 that is mutated in colorectal cancers. , 1991, Science.

[16]  P. O'Connell,et al.  A major segment of the neurofibromatosis type 1 gene: cDNA sequence, genomic structure, and point mutations , 1990, Cell.

[17]  M. Leppert,et al.  Multiple mutations in highly conserved residues are found in mildly affected cystic fibrosis patients , 1990, Cell.

[18]  Horacio Rivera,et al.  A constitutional 5q23 deletion. , 1990, Journal of medical genetics.

[19]  H. Pitot,et al.  A dominant mutation that predisposes to multiple intestinal neoplasia in the mouse. , 1990, Science.

[20]  T. Sekiya,et al.  Rapid and sensitive detection of point mutations and DNA polymorphisms using the polymerase chain reaction. , 1989, Genomics.

[21]  T. Sekiya,et al.  Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[22]  Y. Nakamura,et al.  The gene for familial polyposis coli maps to the long arm of chromosome 5. , 1987, Science.

[23]  F. C. Lucibello,et al.  Localization of the gene for familial adenomatous polyposis on chromosome 5 , 1987, Nature.

[24]  B. Kerem Identification of the cystic fibrosis gene: genetic analysis , 1989 .