Repositorio
Institucional

Hirata, Thiago Dominguez Crespo

Borges, Jessica Bassani

Oliveira, Victor Fernandes

Dagli-Hernandez, Carolina

Ferreira, Glaucio Monteiro

Barbosa, Thais Kristini Almendros Afonso

Marcal, Elisangela da Silva Rodrigues

Los, Bruna

Malaquias, Vanessa Barbosa

Bortolin, Raul Hernandes

Freitas, Renata Caroline Costa

Mori, Augusto Akira

Bastos, Gisele Medeiros

Goncalves, Rodrigo Marques

Araujo, Daniel Branco

Zatz, Henry

Bertolami, Adriana

Faludi, Andre Arpad

Bertolami, Marcelo Chiara

Souza, Amanda Guerra de Moraes Rego

Franca, Joao Italo Dias

Thurow, Helena Strelow

Nakaya, Helder Takashi Imoto

Jannes, Cinthia Elim

Pereira, Alexandre da Costa

Silbiger, Vivian Nogueira

Luchessi, Andre Ducati

Araujo, Jessica Nayara Goes

Nakazone, Marcelo Arruda

Carmo, Tayanne Silva

Souza, Doroteia Rossi Silva

Moriel, Patricia

Wang, Jaqueline Yu Ting

Naslavsky, Michel Satya

Gorjao, Renata

Pithon-Curi, Tania Cristina

Curio, Rui

Fajardo, Cristina Moreno

Wang, Hui-Tzu Lin

Garofalo, Adriana Regina

Cerda, Alvaro

Sampaio, Marcelo Ferraz

Hirata, Rosario Dominguez Crespo

Hirata, Mario Hiroyuki

Identification of pathogenic variants in the Brazilian cohort with Familial hypercholesterolemia using exon-targeted gene sequencing

ELSEVIER

GENE

en

Familial hypercholesterolemia (FH) is a monogenic disease characterized by high plasma low-density lipoprotein cholesterol (LDL-c) levels and increased risk of premature atherosclerotic cardiovascular disease. Mutations in FH-related genes account for 40% of FH cases worldwide. In this study, we aimed to assess the pathogenic variants in FH-related genes in the Brazilian FH cohort FHBGEP using exon-targeted gene sequencing (ETGS) strategy. FH patients (n = 210) were enrolled at five clinical sites and peripheral blood samples were obtained for laboratory testing and genomic DNA extraction. ETGS was performed using MiSeq platform (Illumina). To identify deleterious variants in LDLR, APOB, PCSK9, and LDLRAP1, the long-reads were subjected to Burrows -Wheeler Aligner (BWA) for alignment and mapping, followed by variant calling using Genome Analysis Tool -kit (GATK) and ANNOVAR for variant annotation. The variants were further filtered using in-house custom scripts and classified according to the American College Medical Genetics and Genomics (ACMG) guidelines. A total of 174 variants were identified including 85 missense, 3 stop-gain, 9 splice-site, 6 InDel, and 71 in regu-latory regions (3 & PRIME,UTR and 5 & PRIME,UTR). Fifty-two patients (24.7%) had 30 known pathogenic or likely pathogenic variants in FH-related genes according to the American College Medical and Genetics and Genomics guidelines. Fifty-three known variants were classified as benign, or likely benign and 87 known variants have shown un-certain significance. Four novel variants were discovered and classified as such due to their absence in existing databases. In conclusion, ETGS and in silico prediction studies are useful tools for screening deleterious variants and identification of novel variants in FH-related genes, they also contribute to the molecular diagnosis in the FHBGEP cohort.

2023

artículo original

10.1016/j.gene.2023.147501

PDF

Familial hypercholesterolemia

Exon-targeted gene sequencing

Molecular diagnosis

Single nucleotide variant

Brazilian cohort

Genética y herencia

Hipercolesterolemia familiar

Secuenciación de genes dirigidos a exones

Diagnóstico molecular

Variante de un solo nucleótido

cohorte brasileña

artículo original

versión publicada

metadata

metadata

WOS:001017384000001

0378-1119

hibrida

Genética y herencia

FAPESP 2016/12899-6

CNPQ 447120/2014-0

CAPES 001