Pathogenic mutations in the three known genes - the @entity477 ( @entity477 ), @entity3666 ( @entity3666 ), @entity3667 ( @entity3667 ) - are known to cause @entity195 ( @entity195 ) and tend to be associated with early-onset @entity195 . However, the frequency and risk associated with these mutations vary widely. In addition, mutations in the @entity747 ( @entity747 ) genes - the @entity3668 ( @entity3668 ), @entity21864 ( @entity21864 ) - have also been found to be associated with clinical @entity195 . Here, we conducted targeted resequencing of the exons in genes encoding @entity477 , @entity3666 , @entity3667 , @entity21864 , and @entity3668 in 183 individuals from families with four or more affected relatives, presumed to be @entity195 , and living in the Dominican Republic and Puerto Rico. We then performed linkage and family-based association analyses in carrier families, and genotyped 498 similarly aged unrelated controls from the same ethnic background. Twelve potentially pathogenic mutations were found to be associated with disease in 53 individuals in the five genes. The most frequently observed mutation was the @entity68275 variant in @entity3666 present in 30 (57%) of those sequenced. In the combined linkage and association analyses several rare variants were associated with @entity303 . In Caribbean Hispanics with familial @entity195 , potentially pathogenic variants were present in 29.2%, four were novel mutations, while eight had been previously observed. In addition, some family members carried variants in the @entity21864 and @entity3668 genes which are associated with @entity747 .

Disease-related mutations among Caribbean Hispanics with XXXX .

@entity303 :: ('MESH:D003704', 'Disease') :: ['dementia'] @entity3667 :: ('5664', 'Gene') :: ['PSEN2', 'presenilin 2'] @entity3666 :: ('5663', 'Gene') :: ['presenilin 1', 'PSEN1'] @entity477 :: ('351', 'Gene') :: ['APP', 'amyloid precursor protein'] @entity747 :: ('MESH:D057174', 'Disease') :: ['frontotemporal lobar degeneration', 'FTLD'] @entity21864 :: ('2896', 'Gene') :: ['granulin', 'GRN'] @entity68275 :: ('p|SUB|G|206|A', 'ProteinMutation') :: ['p.Gly206Ala'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "familial Alzheimer's disease"] @entity3668 :: ('4137', 'Gene') :: ['MAPT', 'microtubule-associated protein tau']
@entity303 :: (MESH:D003704,Disease) :: ['familial dementia']
