We report the clinicopathological, genetic, and immunohistochemical 
characterization of an atypical Turcot syndrome (TS) family with small bowel 
cancer. The tumor family history of a patient with cafè-au-lait spots (CALS) and 
early onset adenomas, duodenal cancer, and glioblastoma was positive for colonic 
adenoma (mother), jejunal (maternal grandfather), lung (father), and colorectal 
(paternal uncle) cancers. PMS2 genetic testing identified the nonsense 1951C>T 
(Q643X) and the missense 161C>T (S46I) mutations. PMS2 expression was absent in 
the proband's duodenal cancer with high microsatellite instability. The normal 
cells also displayed no PMS2 expression and some degree of instability. Our 
findings point out the association between PMS2 and TS, and support the 
hypothesis that patients with a few polyps, small bowel tumors with a very early 
onset, glioblastoma, and CALS should be considered as a variant of hereditary 
nonpolyposis colorectal cancer. A recessive model of inheritance caused by 
compound heterozygous mutations was consistent with the observed severe clinical 
phenotype and has important implications for predicting cancer risk in both the 
proband and his relatives.