title: Phenotype-genotype correlations in an extended family with adenomatosis coli and an unusual APC gene mutation.
abstract: OBJECTIVE
  Genotype-phenotype correlations in familial adenomatous polyposis are only partially understood and, in particular, little is known about the biomolecular characteristics of desmoid tumors, which are one of the most serious and frequent manifestations of familial adenomatous polyposis. In the present study, we describe a family with familial adenomatous polyposis, with peculiar clinical characteristics (i.e., frequency and severity of desmoid neoplasms) associated with an unusual mutation of the adenomatosis polyposis coli gene. If confirmed by other investigations, these findings might help to understand the biologic mechanisms by which specific adenomatosis polyposis coli mutations predispose to desmoid tumors.
  
  
  METHODS
  The family with familial adenomatous polyposis, living in southern Italy, was studied from 1985 to the end of 1999; at this date, 15 individuals have been affected by histologically verified familial adenomatous polyposis, 11 of whom had desmoid tumors. A total of 19 family members were studied for adenomatosis polyposis coli gene mutations; 13 of them tested positive and 6 negative. The analytical procedure-previously described-consisted of the extraction of peripheral blood cell DNA, amplification of exon 15 by polymerase chain reaction, single-strand conformation polymorphism analysis, and direct sequencing of the DNA fragment containing the mutation.
  
  
  RESULTS
  The main clinical features of the family were 1) a high frequency of desmoid tumors and, consequently, a high penetrance of the desmoid trait in all branches of the family and in 11 (73.3 percent) of 15 affected individuals and 2) severity of desmoids in at least 4 family members, 2 of whom died for causes related to the presence of these tumors. The molecular basis of the disease was an uncommon mutation of the adenomatosis polyposis coli gene, consisting of a large deletion of 310 base pairs at codon 1,464, with duplication of the breakpoint (4,394ins15del310), leading to a stop codon at position 1,575.
  
  
  CONCLUSIONS
  The present study shows that a truncating mutation in the adenomatosis polyposis coli gene at the beginning of the region frequently associated with desmoids induced a familial adenomatous polyposis phenotype featured by a high penetrance of the desmoid trait, with severe disease in several affected members of both sexes. The study may help to understand the biologic mechanisms of genotype-phenotype correlations in adenomatosis coli.
authors.affiliation: Dipartimento di Medicina Interna, Università di Modena, Modena, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ponz de Leon
authors.forename: L
authors.initials: L
authors.lastname: Varesco
authors.forename: P
authors.initials: P
authors.lastname: Benatti
authors.forename: R
authors.initials: R
authors.lastname: Sassatelli
authors.forename: P
authors.initials: P
authors.lastname: Izzo
authors.forename: M I
authors.initials: MI
authors.lastname: Scarano
authors.forename: G B
authors.initials: GB
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Di Gregorio
authors.forename: V
authors.initials: V
authors.lastname: Gismondi
authors.forename: A
authors.initials: A
authors.lastname: Percesepe
authors.forename: M
authors.initials: M
authors.lastname: de Rosa
authors.forename: L
authors.initials: L
authors.lastname: Roncucci
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005350:Fibroma / Q000235:genetics* / Q000473:pathology; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational