An unexpected Cowden syndrome case found among members of a large familial adenomatous polyposis kindred.
Genetic testing is now considered the standard of care in the management of familial adenomatous polyposis (FAP). Non-carriers of mutations are excluded from endoscopic surveillance. During the systematic screening of the relatives of an affected member with FAP, one non-carrier of APC mutations was unexpectedly found with the typical Cowden syndrome phenotype. One large Algerian family with FAP was screened for an APC germline mutation. Moreover, we also performed a mutation search in the Cowden syndrome member for PTEN, BMPR1A or MADH4 (SMAD4) germline mutations. We identified a mutation in the APC gene that results in a truncated protein (Y935X) in the FAP proband, and subsequently in 12 FAP-affected members. Among the 12 APC mutation-negative members of this family, we found one member with the Cowden disease phenotype. However, the mutation analysis in the PTEN gene and the two other genes involved in juvenile polyposis, namely BMPR1A and MADH4 (SMAD4), in the Cowden syndrome patient failed to show any pathogenic mutation. Genetic testing is a powerful tool that can provide a definitive diagnosis for FAP. However, not all polyposes in the FAP family are adenomatous polyposes.
Mehenni
Hamid
H
Department of Cell Biology, University of Geneva, Switzerland. mehenni@cellbio.unige.ch
Friedl
Wiltraut
W
Nelen
Marcel R
MR
Hutter
Pierre
P
Brundler
Marie A
MA
D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D017491:Genes, APC; D005820:Genetic Testing / Q000379:methods; D018095:Germ-Line Mutation; D006223:Hamartoma Syndrome, Multiple / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree