A novel deletion in progranulin gene is associated with FTDP-17 and CBS.

In the last decade familial frontotemporal dementia (FFTD) has emerged as a distinct clinical disease entity characterized by clinical and genetic heterogeneity. Here, we provide an extensive clinical and genetic characterization of two Italian pedigrees presenting with FFTD (FAM047: 5 patients, 5 unaffected; FAM071: 4 patients, 11 unaffected). Genetic analysis showed a conclusive linkage (LOD score for D17S791/D17S951: 4.173) to chromosome 17 and defined a candidate region containing MAPT and PGRN genes. Recombination analysis assigned two different disease haplotypes to FAM047 and FAM071. In affected subjects belonging to both families, we identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. The age-related penetrance was gender dependent. Both mutations in MAPT and PGRN genes are associated with highly variable clinical phenotypes. Despite the profound differences in the biological functions of the encoded proteins, it is not possible to define a clinical phenotype distinguishing the disease caused by mutations in MAPT and PGRN genes.

Areas of intervention for genetic counselling of dementia: cross-cultural comparison between Italians and Americans.

OBJECTIVE: Purposes of this study are: (1) to evaluate attitudes, beliefs and experiences towards dementia among relatives of Italian familial cases; (2) to perform a cross-cultural comparison between Italian and American samples; (3) to identify predictors of intentions to undergo hypothetical genetic testing. METHODS: Participants were 134 relatives of patients affected by familial forms of dementia. We administered tests measuring health psychological styles, social variables, illness perceptions, intentions regarding genetic testing, and perceptions of the pros and cons of genetic testing. RESULTS: Respondents had a poor Alzheimer's disease knowledge and a low perceived dementia threat. When compared to Americans, Italians reported greater willingness to undergo genetic testing and perceived a different subset of benefits and risks. The strongest predictors of test intention were decisional balance, homemaker status and two beliefs concerning dementia causes. CONCLUSIONS: Italians had a poor knowledge of the disease and a low awareness of personal risk of developing dementia. As compared to Americans, they expressed higher intentions to undergo genetic testing and they have a different perception of benefits and risks. PRACTICE IMPLICATIONS: Understanding of cultural differences in knowledge, attitudes and perception of the disease is important to design optimal health services and education programs for dementia.