caa a22 4500 397573197 CHVBK 20180308164847.0 cr unu---uuuuu 161202e199612 xx s 000 0 eng 10.1093/hmg/5.12.1921 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.12.1921 Familial Infiltrative Fibromatosis (Desmoid Tumours) (MIM135290) Caused by a Recurrent 3′ APC Gene Mutation [Elektronische Daten] [Rodney J. Scott, Nicola J. Froggatt, Richard C. Trembath, D. Gareth R. Evans, Shirley V. Hodgson, Eamonn R. Maher] Desmoid tumours are generally very rare but occur about 100 times more frequently in the colorectal cancer predisposition syndrome familial adenomatous polyposis (MIM 175100), being represented in about 10% of patients. In addition to desmoid disease occurring in familial adenomatous polyposis (FAP) there exist familial infiltrative fibromatosis (MIM 135290) kindreds where there is no evidence of FAP. Previously we have described a kindred with familial infiltrative fibromatosis (FIF) in which desmoid tumours were associated with nonpolyposis colorectal cancer. FAP is caused by mutations in the APC gene and various genotype-phenotype relationships have been defined including reports that colorectal polyposis is less severe with mutations 5′ to codon 157 and that the risk of desmoid tumours is high in FAP patients with APC gene mutations between codons 1444 and 1598. There is relatively little information on the phenotype of APC gene mutations 3′ to codon 1598; however, one large family has been reported with a mutation at codon 1987 which presents with a highly variable phenotype which includes desmoid disease. We screened our original FIF kindred and three further families with a similar phenotype for mutations in the APC gene. A 4 bp frameshift deletion in codon 1962 was identified in the original FIF kindred and two further apparently unrelated families. Haplotype analysis suggests a common origin for the APC mutation in all three families. Affected individuals had no evidence of congenital hypertrophy of the retinal pigment epithelium. Colorectal polyposis was variable, and most affected patients had either none or a few late onset polyps. These findings demonstrate (i) that FAP and FIF are allelic, and (ii) that APC gene mutations which truncate the APC protein distal to the beta-catenin binding domain are associated with desmoid tumours, absent CHRPE and variable but attenuated polyposis expression. © 1993 Oxford University Press Scott Rodney J. Human Genetics, Department of Research, University Clinics, Basle CH-4031, Switzerland aut Froggatt Nicola J. Cambridge University Department of Pathology, Cambridge, UK aut Trembath Richard C. Departments of Genetics and Medicine, University of Leicester, Leicester, UK aut Evans D. Gareth R. Department of Medical Genetics, St Mary's Hospital, Manchester, UK aut Hodgson Shirley V. Division of Medical and Molecular Genetics, United Medicals Schools, Guy's Hospital, London, UK aut Maher Eamonn R. Cambridge University Department of Pathology, Cambridge, UK aut Human Molecular Genetics Oxford University Press 5/12(1996-12), 1921-1924 0964-6906 5:12<1921 1996 5 hmg https://doi.org/10.1093/hmg/5.12.1921 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.12.1921 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Scott Rodney J. Human Genetics, Department of Research, University Clinics, Basle CH-4031, Switzerland aut NATIONALLICENCE 700 1- Froggatt Nicola J. Cambridge University Department of Pathology, Cambridge, UK aut NATIONALLICENCE 700 1- Trembath Richard C. Departments of Genetics and Medicine, University of Leicester, Leicester, UK aut NATIONALLICENCE 700 1- Evans D. Gareth R. Department of Medical Genetics, St Mary's Hospital, Manchester, UK aut NATIONALLICENCE 700 1- Hodgson Shirley V. Division of Medical and Molecular Genetics, United Medicals Schools, Guy's Hospital, London, UK aut NATIONALLICENCE 700 1- Maher Eamonn R. Cambridge University Department of Pathology, Cambridge, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/12(1996-12), 1921-1924 0964-6906 5:12<1921 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford