title: Effectiveness of screening for known mutations in Sicilian patients with "probable" familial hypercholesterolemia.
abstract: OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Department of Internal Medicine, University of Palermo, Italy.
authors.forename: A B
authors.initials: AB
authors.lastname: Cefalù
authors.forename: G
authors.initials: G
authors.lastname: Emmanuele
authors.forename: G
authors.initials: G
authors.lastname: Marino
authors.forename: B
authors.initials: B
authors.lastname: Fiore
authors.forename: R
authors.initials: R
authors.lastname: Caldarella
authors.forename: N
authors.initials: N
authors.lastname: Vivona
authors.forename: D
authors.initials: D
authors.lastname: Noto
authors.forename: C M
authors.initials: CM
authors.lastname: Barbagallo
authors.forename: S
authors.initials: S
authors.lastname: Costa
authors.forename: M C
authors.initials: MC
authors.lastname: Gueli
authors.forename: S
authors.initials: S
authors.lastname: Bertolini
authors.forename: A
authors.initials: A
authors.lastname: Notarbartolo
authors.forename: S
authors.initials: S
authors.lastname: Travali
authors.forename: M R
authors.initials: MR
authors.lastname: Averna
mesh_terms: D015331:Cohort Studies; D005091:Exons; D005787:Gene Frequency; D005820:Genetic Testing / Q000191:economics; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011973:Receptors, LDL / Q000235:genetics*; D012802:Sicily
chemical_list: D011973:Receptors, LDL