Hereditary desmoid disease in a family with a germline Alu I repeat mutation of the APC gene

Two families with autosomal dominantly inherited desmoid tumors have recent ly been shown to have germline mutations at the 3' end of the APC gene. We subsequently identified an Amish family with autosomal dominantly inherited desmoid tumors, Genetic analysis performed on one family member, a 47-year -old man with multiple desmoid tumors and no colon polyps, revealed a prote in truncating mutation in the middle of the APC gene. The truncating mutati on is the result of a 337-bp insertion of an Alu I sequence into codon 1526 of the APC gene. The presence of a poly(A) tail at the 3' end of the inser tion suggests that the Alu I sequence was inserted by a retrotranspositiona l event. Germline insertions of Alu/sequences have occasionally been report ed to cause other genetic diseases including type 1 neurofibromatosis, here ditary site-specific breast cancer (BRCA2), and hemophilia B. However, this is the first report of a germline mutation of the APC gene resulting from an Alu I insertion.