title: Familial hypercholesterolemia in Brazil: cascade screening program, clinical and genetic aspects.
abstract: BACKGROUND
  There is little knowledge about familial hypercholesterolemia in Brazil. This study presents the first results of genetic cascade screening performed in the city of Sao Paulo.
  
  
  METHODS
  Two-hundred and forty-eight suspected index cases were initially included. DNA was extracted from peripheral blood and the complete coding sequence of low-density lipoprotein receptor, exon 7 of proprotein convertase subtilisin/kexin type 9 gene and part of exon 26 of apolipoprotein B genes were sequenced. Multiplex Ligation-dependent Probe Amplification was performed on cases where a causal mutation was not identified through sequencing. After the identification of a causal mutation screening in first-degree relatives was pursued.
  
  
  RESULTS
  From 248 index cases, a mutation was found in 125 individuals (50.4%). 394 relatives were included in the cascade screening program and a mutation was identified in 59.4%. Seventy different causal mutations in the low-density lipoprotein receptor gene (97.2%) and 2 in the apolipoprotein B gene (2.8%) were found. No mutations were encountered in the proprotein convertase subtilisin/kexin type 9 gene. Mutations in exons 14 and 4 were the most prevalent and, 10 cases of true homozygotes (8 index cases and 2 relatives) and 1 compound heterozygote were identified. The most frequent mutation found was of Lebanese origin, the p.(Cys681*) mutation in exon 14 (8.5%).
  
  
  CONCLUSIONS
  Genetic familial hypercholesterolemia cascade screening is feasible in Brazil and leads to identification of a mutation in approximately half of the index cases with higher rates of success in their relatives.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil. Electronic address: cejannes@hotmail.com.
authors.forename: Cinthia E
authors.initials: CE
authors.lastname: Jannes
authors.affiliation: Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Raul D
authors.initials: RD
authors.lastname: Santos
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Pãmela R
authors.initials: PR
authors.lastname: de Souza Silva
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Luciana
authors.initials: L
authors.lastname: Turolla
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Ana C M
authors.initials: AC
authors.lastname: Gagliardi
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Julia D C
authors.initials: JD
authors.lastname: Marsiglia
authors.affiliation: Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Ana P
authors.initials: AP
authors.lastname: Chacra
authors.affiliation: Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Marcio H
authors.initials: MH
authors.lastname: Miname
authors.affiliation: Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Viviane Z
authors.initials: VZ
authors.lastname: Rocha
authors.affiliation: Lipid Clinic, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Wilson Salgado
authors.initials: WS
authors.lastname: Filho
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Jose E
authors.initials: JE
authors.lastname: Krieger
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D015992:Body Mass Index; D001938:Brazil / Q000453:epidemiology; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D007861:Lebanon; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D009154:Mutation; D011237:Predictive Value of Tests; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: D001055:Apolipoproteins B; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Apolipoprotein B; Cascade screening; Familial hypercholesterolemia; Index patient; Low density lipoprotein receptor; Mutations