Molecular Basis of Familial Hypercholesterolemia in Brazil: Identification of Seven Novel LDLR Gene Mutations

Autor(es)

Salazar, Luis A. ^{[1, 2]} ; Hirata, Mario H. ; Cavalli, Selma A. ; Nakandakare, Edna R. ^[3] ; Forti, Neusa ^[4] ; Diament, Jaime ^[4] ; Giannini, Sergio D. ^[4] ; Bertolami, Marcelo C. ^[5] ; Hirata, Rosario D. C.

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo - Brazil

^[2] Univ La Frontera, Fac Med, Temuco - Chile

^[3] Univ Sao Paulo, Serv Endocrinol, BR-05508900 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05508900 Sao Paulo - Brazil

^[5] Dante Pazzanese Cardiol Inst, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Human mutation; v. 19, n. 4, p. 462-463, 2002.
• Citações Web of Science: 16

Resumo

Low-density lipoprotein receptor (LDLR) gene mutations cause familial hypercholesterolemia (FH), one of the most common single gene disorders. The spectrum of LDLR mutations in Brazil is not known. The aim of this study was the characterization of LDLR mutations in 35 unrelated Brazilian patients with heterozygous FH. The promoter region, the 18 exons and the flanking intron sequences of the LDLR gene were screened by PCR-SSCP analysis and by DNA sequencing. In addition, we have screened the apolipoprotein B gene (APOB) for known mutations (R3500Q and R3531C) that cause Familial defective apo B-100 (FDB) by PCR-RFLP procedure. We found two nonsense (E92X and C371X) and six missense LDLR mutations (R236W, G322S, G352D, A370T, C675W and C677Y), that were previously described in FH patients from other populations. We also found five novel missense [G(-20) R, T476P, V503G, D580H and S652R] and two novel frame shift LDLR mutations (FsR757 and FsS828). Four patients were found to carry two different mutations in the LDLR gene: G352D and A370T (one patient), S652R and C675W (one patient) and T476P and V503G (two patients). APOB mutations were not found. These findings demonstrate that there is a broad spectrum of mutations in the LDLR gene in FH individuals from Brazil. (C) 2002 Wiley-Liss, Inc. (AU)

• Processo FAPESP: 98/09759-8 - Análise do polimorfismo genético e expressão do receptor da LDL em indivíduos hipercolesterolêmicos
• Beneficiário: Luis Antonio Salazar Navarrete
• Modalidade de apoio: Bolsas no Brasil - Doutorado