Identification and surveillance of 19 XXXX families in southern Italy: report of six novel germline mutations and a common founder mutation.

@entity1 @entity6756 @entity72352 @entity124 @entity4309 @entity72353 @entity5 @entity4311 @entity14437 @entity14 @entity4638
@entity4309 ( @entity4309 ), or @entity14 ( @entity14 ), is an autosomal dominant condition responsible for early onset @entity5 mostly in the colonrectum and endometrium as well as in other organ sites. @entity4309 is caused by germline mutations in mismatch repair genes, prevalently in @entity4311 , @entity6756 , and less frequently in @entity4638 and @entity14437 . Twenty-nine non-related index cases with @entity14 ( @entity14 ) were collected from a region in southeast Italy (Apulia). Among this set of @entity1 , fifteen fulfilled the Amsterdam criteria II. The presence of @entity5 @entity124 ( @entity124 ) was assessed in all index cases and 19 (15 AC+/4 AC-) were classified as @entity124 . Mutation analysis performed on all @entity1 , identified 15 pathogenic mutations in @entity72352 in @entity4311 . 4/15 mutations in @entity72353 /4 @entity4311 mutations have not been previously reported. Three previously reported mutations were further investigated for the possibility of a common founder effect. Genetic counseling was offered to all probands and extended to 183 relatives after molecular testing and 85 (46%) mutation carriers were identified. Eighty mutation carriers underwent an accurate clinical and instrumental surveillance protocol. Our results confirm that the identification of @entity4309 @entity1 based exclusively on family history may miss @entity1 carrying germline mutations in the MMR genes. Moreover, our results demonstrated that molecular screening and subsequent instrumental surveillance are very effective in identifying CRCs at earlier stages and reducing the number of deaths from secondary cancers in @entity14 @entity1 .
