Whole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome

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dc.creatorVictor Borda
dc.creatorAdriana Melo
dc.creatorMaria Elisabeth Moreira
dc.creatorLetícia Guida
dc.creatorDaniela P. Cunha
dc.creatorLeonardo Gomes
dc.creatorZilton Vasconcelos
dc.creatorFabio Faucz
dc.creatorAmilcar Tanuri
dc.creatorConstantine Stratakis
dc.creatorRenato Santana de Aguiar
dc.creatorRonaldo da Silva Francisco Junior
dc.creatorCynthia Chester Cardoso
dc.creatorAna Tereza Ribeiro de Vasconcelos
dc.creatorJoseane B. Carvalho
dc.creatorGuilherme L. Morais
dc.creatorÁtila Duque Rossi
dc.creatorPaula Pezzuto
dc.creatorGirlene S. Azevedo
dc.creatorBruno Luiz Fonseca Schamber-Reis
dc.creatorElyzabeth Avvad Portari
dc.date.accessioned2023-07-17T18:03:00Z
dc.date.accessioned2025-09-08T23:30:57Z
dc.date.available2023-07-17T18:03:00Z
dc.date.issued2021
dc.identifier.doihttps://doi.org/10.1371/journal.pntd.0009507
dc.identifier.issn1935-2735
dc.identifier.urihttps://hdl.handle.net/1843/56416
dc.languagepor
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofPLOS Neglected Tropical Diseases
dc.rightsAcesso Aberto
dc.subjectVírus da Zika
dc.subject.otherZika
dc.subject.otherGenetic
dc.titleWhole-exome sequencing reveals insights into genetic susceptibility to Congenital Zika Syndrome
dc.typeArtigo de periódico
local.citation.epage17
local.citation.issue6
local.citation.spage1
local.citation.volume15
local.description.resumoCongenital Zika Syndrome (CZS) is a critical illness with a wide range of severity caused by Zika virus (ZIKV) infection during pregnancy. Life-threatening neurodevelopmental dysfunctions are among the most common phenotypes observed in affected newborns. Risk factors that contribute to susceptibility and response to ZIKV infection may be related to the virus itself, the environment, and maternal genetic background. Nevertheless, the newborn’s genetic contribution to the critical illness is still not elucidated. Here, we aimed to identify possible genetic variants as well as relevant biological pathways that might be associated with CZS phenotypes. For this purpose, we performed a whole-exome sequencing in 40 children born to women with confirmed exposure to ZIKV during pregnancy. We investigated the occurrence of rare harmful single-nucleotide variants (SNVs) possibly associated with inborn errors in genes ontologically related to CZS phenotypes. Moreover, an exome-wide association analysis was also performed using a case-control design (29 CZS cases and 11 controls), for both common and rare variants. Five out of the 29 CZS patients harbored known pathogenic variants likely to contribute to mild to severe manifestations observed. Approximately, 30% of affected individuals carried at least one pathogenic or likely pathogenic SNV in genes candidates to play a role in CZS. Our common variant association analysis detected a suggestive protective effect of the rs2076469 in DISP3 gene (p-value: 1.39 x 10−5). The IL12RB2 gene (p-value: 2.18x10-11) also showed an unusual distribution of nonsynonymous rare SNVs in control samples. Finally, genes harboring harmful variants are involved in processes related to CZS phenotypes such as neurological development and immunity. Therefore, both rare and common variations may be likely to contribute as the underlying genetic cause of CZS susceptibility. The variations and pathways identified in this study may also have implications for the development of therapeutic strategies in the future.
local.identifier.orcidhttps://orcid.org/0000-0003-3209-3961
local.identifier.orcidhttps://orcid.org/0000-0002-8575-544X
local.identifier.orcidhttps://orcid.org/0000-0002-2034-0294
local.identifier.orcidhttps://orcid.org/0000-0003-3543-1532
local.identifier.orcidhttps://orcid.org/0000-0002-1721-0608
local.identifier.orcidhttps://orcid.org/0000-0002-2193-2224
local.identifier.orcidhttps://orcid.org/0000-0001-7959-9842
local.identifier.orcidhttps://orcid.org/0000-0003-0570-750X
local.identifier.orcidhttps://orcid.org/0000-0002-4058-5520
local.identifier.orcidhttps://orcid.org/0000-0001-5180-3717
local.identifier.orcidhttps://orcid.org/0000-0003-0565-7047
local.identifier.orcidhttps://orcid.org/0000-0001-6235-8807
local.identifier.orcidhttps://orcid.org/0000-0001-9570-8244
local.identifier.orcidhttps://orcid.org/0000-0002-7640-1463
local.identifier.orcidhttps://orcid.org/0000-0003-2372-0898
local.identifier.orcidhttps://orcid.org/0000-0003-2372-0898
local.publisher.countryBrasil
local.publisher.departmentICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
local.publisher.initialsUFMG
local.url.externahttps://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009507

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