Cascade screening and genetic diagnosis of familial hypercholesterolemia in clusters of the Southeastern region from Bra
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ORIGINAL ARTICLE
Cascade screening and genetic diagnosis of familial hypercholesterolemia in clusters of the Southeastern region from Brazil Júnea Paolucci de Paiva Silvino1 · Cinthia Elim Jannes2 · Mauricio Teruo Tada2 · Isabella Ramos Lima2 · Iêda de Fátima Oliveira Silva3 · Alexandre Costa Pereira2 · Karina Braga Gomes1,3 Received: 14 September 2020 / Accepted: 16 November 2020 / Published online: 24 November 2020 © Springer Nature B.V. 2020
Abstract Familial hypercholesterolemia (FH) is an autosomal dominant genetic disease characterized by high levels of low-density lipoprotein-cholesterol (LDLc), associated to premature cardiovascular disease. The detection of the variants related to FH is important to improve the early diagnosis in probands / index-cases (ICs) and their relatives. We included ICs with FH and their relatives, living in a small region of Minas Gerais state-Brazil, which were classified according to Dutch Lipid Clinic Network Criteria (DLCNC) and submitted to sequencing of genes related to FH (LDLR, APOB, PCSK9, LDLRAP1, LIPA, STAP1, APOE, ABCG5 e ABCG8). In a total of 143 subjects (32 ICs and 111 relatives), eight variants were identified in 91 individuals. From these variants, five were in LDLR [p.(Asp224Asn), p.(Ser854Gly), p.(Cys34Arg), p.(Asp601His), deletion of exon15 in LDLR)], one in APOB [p.(Met499Val)], one in PCSK9 [p.(Arg237Trp)] and one in APOE [p.(Pro28Leu)] genes. The variants were detected in 100% of those subjects classified as definitive, 87% as probable and 69% as possible FH cases based on DLCNC. The LDLc level was higher in individuals with corneal arch and xanthomas or xanthelasmas, as well as in pathogenic or probably pathogenic variants carriers. This study showed higher frequency of LDLR gene variants compared to other genes related to LDL metabolism in individuals with FH in Minas Gerais – Brazil and the presence of FH in relatives without previous diagnosis. Our data reinforce the importance of molecular and clinical evaluation of FH relatives in order to early diagnosis the FH, as well as cardiovascular diseases prevention. Keywords Familial hypercholesterolemia · Genetic variants · LDL · Cardiovascular disease
Introduction
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-06014-0) contains supplementary material, which is available to authorized users. * Karina Braga Gomes [email protected] 1
Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerias, Brazil
2
Laboratório de Genética e Cardiologia Molecular do Instituto do Coração de São Paulo (INCOR), Hospital das Clínicas da Universidade de São Paulo, São Paulo, Brazil
3
Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 Pampulha, Belo Horizonte, Minas Gerais, Brazil
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that affects low-density lipoprotein cholesterol (LDLc) metabolism. Most of the variants are in the LDL receptor (LDLR) gene [1], an
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