+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Phenotype-genotype correlations in an extended family with adenomatosis coli and an unusual APC gene mutation

Phenotype-genotype correlations in an extended family with adenomatosis coli and an unusual APC gene mutation

Diseases of the Colon and Rectum 44(11): 1597-1604

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. 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. 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. 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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 046973730

Download citation: RISBibTeXText

PMID: 11711730

DOI: 10.1007/bf02234378

Related references

Exome sequencing identifies a c.148-1G>C mutation of TBX5 in a Holt-Oram family with unusual genotype-phenotype correlations. Cellular Physiology and Biochemistry 37(3): 1066-1074, 2015

Clinical features and genotype-phenotype correlations in 41 Italian families with adenomatosis coli. Italian Journal of Gastroenterology and Hepatology 31(9): 850-860, 1999

A novel ferritin light chain gene mutation in a Japanese family with neuroferritinopathy: description of clinical features and implications for genotype-phenotype correlations. Movement Disorders 24(3): 441-445, 2009

Exploring Phenotype-Genotype Correlations Using Interstitial Glucose Results in a Family With a Glucokinase Mutation. Journal of Diabetes Science and Technology 12(6): 1248-1249, 2018

Codon 200 mutation of the prion gene: genotype-phenotype correlations. Journal of Neurology 259(12): 2579-2584, 2012

Genotype-phenotype correlations at the adenomatous polyposis coli (APC) gene. Critical Reviews in Oncogenesis 6(3-6): 291-303, 1995

Noonan syndrome PTPN11 gene mutation and phenotype/genotype correlations The French experience. American Journal of Human Genetics 73(5): 275, 2003

Amelogenesis imperfecta due to a mutation of the enamelin gene: clinical case with genotype-phenotype correlations. Pediatric Dentistry 32(1): 56-60, 2010

Long-term follow-up of patients with recessive dystrophic epidermolysis bullosa in the Netherlands: expansion of the mutation database and unusual phenotype-genotype correlations. Journal of Dermatological Science 56(1): 9, 2009

Mutations of the Wilsons disease gene in Austria Genotype/phenotype correlations and feasibility of mutation analysis. Gastroenterology 118(4 Suppl 2 Part 2): AASLD A143, 2000

Paramyotonia congenita: Genotype to phenotype correlations in two families and report of a new mutation in the sodium channel gene. Journal of the Neurological Sciences 142(1-2): 126-133, 1996

Genotype-phenotype correlations in individuals with a founder mutation in the MLH1 gene and hereditary non-polyposis colorectal cancer. Scandinavian Journal of Gastroenterology 42(6): 746-753, 2007

Familial Mediterranean fever gene mutation frequencies and genotype-phenotype correlations in the Aegean region of Turkey. Rheumatology International 31(6): 779-784, 2011

Rethinking genotype-phenotype correlations in papillorenal syndrome: a case report on an unusual congenital camptodactyly and skeletal deformity with a heterogeneous PAX2 mutation of hexanucleotide duplication. Gene 641: 74-77, 2018

Molecular analysis of the APC gene in 205 families: extended genotype-phenotype correlations in FAP and evidence for the role of APC amino acid changes in colorectal cancer predisposition. Journal of Medical Genetics 36(1): 14-20, 1999