TY - JOUR
T1 - Effectiveness of screening for known mutations in Sicilian patients with "probable" familial hypercholesterolemia
AU - Averna, Maurizio
AU - Costa, Salvatore
AU - Barbagallo, Carlo Maria
AU - Cefalu', Angelo Baldassare
AU - Vivona, Nicoletta
AU - Cefalù, Angelo B.
AU - Travali, null
AU - Emmanuele, null
AU - Caldarella, Rosalia
AU - Fiore, null
AU - Emmanuele, Giovanni
AU - Noto, Davide
AU - Travali, Salvatore
AU - Bertolini, Stefano
AU - Averna, Maurizio R.
AU - Notarbartolo, Alberto
AU - Barbagallo, Carlo M.
AU - Marino, Giuseppina
AU - Gueli, Maria Concetta
PY - 2001
Y1 - 2001
N2 - Background and Aim: More than 750 mutations in the low-density lipoprotein (LDL) receptor gene are currently known to cause familial hypercholesterolemia (FH), but the array of mutations varies considerably in different populations. The definition of essentially all the LDL receptor gene mutations in a population is therefore a prerequisite for the implementation of nation-wide genetic testing for FH. Methods and Results: In this study, a screening strategy based on PCR-enzymatic digestion and PCR-allele specific hybridisation procedures was used to evaluate the frequency distributions of 11 known mutations in a cohort of 214 unrelated subjects meeting the diagnostic criteria of "probable" FH. We identified 20 mutation carriers (9.3%). One mutation (FH Palermo-1) occurred with a relatively high frequency, accounting for 7% of the entire study cohort. We also report the first observation of the receptor-negative mutation V408M (Afrikaner-2) in Italy. Conclusions: Our screening approach is not effective and, at least in our area, it is not a suitable alternative to the more expensive and time-consuming sequencing approach. However, our data suggest that it is possible to identify the molecular defect in about 10% of Sicilian patients with a clinical diagnosis of "probable FH" using a rapid laboratory diagnostic mutation panel. Four mutations were responsible for all of the diagnosed cases, and it could be reasonable to use this 4-mutation panel as a preliminary step before adopting a more complex laboratory approach. ©2001, Medikal Press.
AB - Background and Aim: More than 750 mutations in the low-density lipoprotein (LDL) receptor gene are currently known to cause familial hypercholesterolemia (FH), but the array of mutations varies considerably in different populations. The definition of essentially all the LDL receptor gene mutations in a population is therefore a prerequisite for the implementation of nation-wide genetic testing for FH. Methods and Results: In this study, a screening strategy based on PCR-enzymatic digestion and PCR-allele specific hybridisation procedures was used to evaluate the frequency distributions of 11 known mutations in a cohort of 214 unrelated subjects meeting the diagnostic criteria of "probable" FH. We identified 20 mutation carriers (9.3%). One mutation (FH Palermo-1) occurred with a relatively high frequency, accounting for 7% of the entire study cohort. We also report the first observation of the receptor-negative mutation V408M (Afrikaner-2) in Italy. Conclusions: Our screening approach is not effective and, at least in our area, it is not a suitable alternative to the more expensive and time-consuming sequencing approach. However, our data suggest that it is possible to identify the molecular defect in about 10% of Sicilian patients with a clinical diagnosis of "probable FH" using a rapid laboratory diagnostic mutation panel. Four mutations were responsible for all of the diagnosed cases, and it could be reasonable to use this 4-mutation panel as a preliminary step before adopting a more complex laboratory approach. ©2001, Medikal Press.
UR - http://hdl.handle.net/10447/184412
M3 - Article
VL - 11
SP - 394
EP - 400
JO - Nutrition, Metabolism and Cardiovascular Diseases
JF - Nutrition, Metabolism and Cardiovascular Diseases
SN - 0939-4753
ER -