title: Analysis of sequence variations in the LDL receptor gene in Spain: general gene screening or search for specific alterations?
abstract: BACKGROUND
  Familial hypercholesterolemia (FH) is a frequent form of autosomal-dominant hypercholesterolemia that predisposes to premature coronary atherosclerosis. FH is caused by sequence variations in the gene coding for the LDL receptor (LDLR). This gene has a wide spectrum of sequence variations, and genetic diagnosis can be performed by 2 strategies.
  
  
  METHODS
  Point variations and large rearrangements were screened along all the LDLR gene (promoter, exons, and flanking intron sequences).
  
  
  RESULTS
  We screened a sample of 129 FH probands from the Valencian Community, Spain, and identified 54 different LDLR sequence variations. The most frequent (10% of cases) was 111insA, and 60% of the variants had a frequency as low as 1%. A previously described method for detection of known sequence variations in the Spanish population by DNA array analysis allowed the identification of only approximately 50% of patients with a variant LDLR gene and approximately 40% of the screened samples.
  
  
  CONCLUSIONS
  Our results indicate that the adequate procedure to identify LDLR sequence variations in outbreed populations should include screening of the entire gene.
authors.affiliation: Laboratorio de Estudios Genéticos, Fundación de Investigación HCUV, Hospital Clínico Universitario de Valencia, Valencia, Spain.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Blesa
authors.forename: Ana Barbara
authors.initials: AB
authors.lastname: Garcia-Garcia
authors.forename: Sergio
authors.initials: S
authors.lastname: Martinez-Hervas
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Mansego
authors.forename: Veronica
authors.initials: V
authors.lastname: Gonzalez-Albert
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Ascaso
authors.forename: Rafael
authors.initials: R
authors.lastname: Carmena
authors.forename: Jose Tomas
authors.initials: JT
authors.lastname: Real
authors.forename: Felipe Javier
authors.initials: FJ
authors.lastname: Chaves
mesh_terms: D001055:Apolipoproteins B / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D011973:Receptors, LDL / Q000235:genetics*; D017422:Sequence Analysis, DNA; D013030:Spain
chemical_list: D001055:Apolipoproteins B; D011973:Receptors, LDL