In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 15, No. 6 ( 2021-6-14), p. e0009507-
Abstract:
Congenital 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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0009507
DOI:
10.1371/journal.pntd.0009507.g001
DOI:
10.1371/journal.pntd.0009507.g002
DOI:
10.1371/journal.pntd.0009507.g003
DOI:
10.1371/journal.pntd.0009507.t001
DOI:
10.1371/journal.pntd.0009507.s001
DOI:
10.1371/journal.pntd.0009507.s002
DOI:
10.1371/journal.pntd.0009507.s003
DOI:
10.1371/journal.pntd.0009507.s004
DOI:
10.1371/journal.pntd.0009507.s005
DOI:
10.1371/journal.pntd.0009507.s006
DOI:
10.1371/journal.pntd.0009507.s007
DOI:
10.1371/journal.pntd.0009507.s008
DOI:
10.1371/journal.pntd.0009507.s009
DOI:
10.1371/journal.pntd.0009507.s010
DOI:
10.1371/journal.pntd.0009507.s011
DOI:
10.1371/journal.pntd.0009507.s012
DOI:
10.1371/journal.pntd.0009507.s013
DOI:
10.1371/journal.pntd.0009507.s014
DOI:
10.1371/journal.pntd.0009507.s015
DOI:
10.1371/journal.pntd.0009507.s016
DOI:
10.1371/journal.pntd.0009507.s017
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2429704-5
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