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. MATERIAL AND 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%). CONCLUSION: 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.
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. MATERIAL AND 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%). CONCLUSION: 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: Roopa Mehta; Rafael Zubirán; Alexandro J Martagón; Alejandra Vazquez-Cárdenas; Yayoi Segura-Kato; María Teresa Tusié-Luna; Carlos A Aguilar-Salinas Journal: J Lipid Res Date: 2016-10-24 Impact factor: 5.922
Authors: Gláucia Maria Moraes de Oliveira; Luisa Campos Caldeira Brant; Carisi Anne Polanczyk; Deborah Carvalho Malta; Andreia Biolo; Bruno Ramos Nascimento; Maria de Fatima Marinho de Souza; Andrea Rocha De Lorenzo; Antonio Aurélio de Paiva Fagundes Júnior; Beatriz D Schaan; Fábio Morato de Castilho; Fernando Henpin Yue Cesena; Gabriel Porto Soares; Gesner Francisco Xavier Junior; Jose Augusto Soares Barreto Filho; Luiz Guilherme Passaglia; Marcelo Martins Pinto Filho; M Julia Machline-Carrion; Marcio Sommer Bittencourt; Octavio M Pontes Neto; Paolo Blanco Villela; Renato Azeredo Teixeira; Roney Orismar Sampaio; Thomaz A Gaziano; Pablo Perel; Gregory A Roth; Antonio Luiz Pinho Ribeiro Journal: Arq Bras Cardiol Date: 2022-01 Impact factor: 2.000
Authors: Abhimanyu Garg; Sergio Fazio; P Barton Duell; Alexis Baass; Chandrasekhar Udata; Tenshang Joh; Tom Riel; Marina Sirota; Danielle Dettling; Hong Liang; Pamela D Garzone; Barry Gumbiner; Hong Wan Journal: J Endocr Soc Date: 2019-11-29