A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation
IntroductionFlaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently...
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2021.530028/full |
| _version_ | 1818607898729644032 |
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| author | Estephania Candelo Estephania Candelo Ana Maria Sanz Diana Ramirez-Montaño Lorena Diaz-Ordoñez Ana Maria Granados Fernando Rosso Julian Nevado Pablo Lapunzina Harry Pachajoa Harry Pachajoa |
| author_facet | Estephania Candelo Estephania Candelo Ana Maria Sanz Diana Ramirez-Montaño Lorena Diaz-Ordoñez Ana Maria Granados Fernando Rosso Julian Nevado Pablo Lapunzina Harry Pachajoa Harry Pachajoa |
| author_sort | Estephania Candelo |
| collection | DOAJ |
| description | IntroductionFlaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. ZIKV became widespread all over Brazil and was linked with potential cases of microcephaly.Case reportWe report a case of a 28-year-old Colombian woman, who came to the Obstetric Department with an assumed conglomerate of fetal abnormalities detected via ultrasonography, which was performed at 29.5 weeks of gestation. The patient presented with multiple abnormalities, which range from a suggested Arnold–Chiari malformation, compromising the lateral and third ventricles, liver calcifications, bilateral pyelocalic dilatations, other brain anomalies, and microcephaly. At 12 weeks of gestation, the vertical transmission of ZIKV was suspected. At 38.6 weeks of gestation, the newborn was delivered, with the weight in the 10th percentile (3,180 g), height in the 10th percentile (48 cm), and cephalic circumference under the 2nd percentile (31 cm). Due to the physical findings, brain magnetic resonance imaging (MRI) was performed, revealing a small and deviated brain stem, narrowing of the posterior fossa, a giant posterior fossa cyst with ventricular dilatation, a severe cortical and white matter thinning, cerebellar vermis with hypoplasia, and superior and lateral displacement of the cerebellum. In addition, hydrocephalus was displayed by the axial sequence, and the cerebral cortex was also compromised with lissencephaly. Schizencephaly was found with left frontal open-lip, and no intracranial calcifications were found. Two novel heterozygous nonsense mutations were identified using whole-exome sequencing, and both are located in exon 8 under the affection of ZIKV congenital syndrome (CZS) that produced a premature stop codon resulting in the truncation of the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) protein.ConclusionWe used molecular and microbiological assessments to report the initial case of vertically transmitted ZIKV infection with congenital syndrome associated with a neurological syndrome, where a mutation in the CDK5RAP2 gene was also identified. The CDK5RAP2 gene encodes a pericentriolar protein that intervenes in microtubule nucleation and centriole attachment. Diallelic mutation has previously been associated with primary microcephaly. |
| first_indexed | 2024-12-16T14:34:04Z |
| format | Article |
| id | doaj.art-28a0456ef58c4753852559ca5fae02c4 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-16T14:34:04Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Genetics |
| spelling | doaj.art-28a0456ef58c4753852559ca5fae02c42022-12-21T22:28:09ZengFrontiers Media S.A.Frontiers in Genetics1664-80212021-03-011210.3389/fgene.2021.530028530028A Possible Association Between Zika Virus Infection and CDK5RAP2 MutationEstephania Candelo0Estephania Candelo1Ana Maria Sanz2Diana Ramirez-Montaño3Lorena Diaz-Ordoñez4Ana Maria Granados5Fernando Rosso6Julian Nevado7Pablo Lapunzina8Harry Pachajoa9Harry Pachajoa10Universidad Icesi, Ear Institute University College London and Fundación Valle del Lili, Cali, ColombiaCenter for Research on Congenital Anomalies and Rare Diseases (CIACER), Department of Basic Medical Sciences, Universidad Icesi, Cali, ColombiaFundacion Valle del Lili, Cali, ColombiaCenter for Research on Congenital Anomalies and Rare Diseases (CIACER), Department of Basic Medical Sciences, Universidad Icesi, Cali, ColombiaCenter for Research on Congenital Anomalies and Rare Diseases (CIACER), Department of Basic Medical Sciences, Universidad Icesi, Cali, ColombiaNeuroradiology Department Fundación Valle del Lili, Cali, ColombiaFundacion Valle del Lili, Cali, ColombiaInstituto de Genética Médica y Molecular (INGEMM), IdiPAZ, HospitalUniversitario La Paz, Madrid, CIBER de Enfermedades Raras (CIBERER), ISCIII, Madrid, SpainInstituto de Genética Médica y Molecular (INGEMM), IdiPAZ, HospitalUniversitario La Paz, Madrid, CIBER de Enfermedades Raras (CIBERER), ISCIII, Madrid, SpainCenter for Research on Congenital Anomalies and Rare Diseases (CIACER), Department of Basic Medical Sciences, Universidad Icesi, Cali, ColombiaGenetics Department, Fundación Valledel Lili, Cali, ColombiaIntroductionFlaviviridae family belongs to the Spondweni serocomplex, which is mainly transmitted by vectors from the Aedes genus. Zika virus (ZIKV) is part of this genus. It was initially reported in Brazil in December 2014 as an unknown acute generalized exanthematous disease and was subsequently identified as ZIKV infection. ZIKV became widespread all over Brazil and was linked with potential cases of microcephaly.Case reportWe report a case of a 28-year-old Colombian woman, who came to the Obstetric Department with an assumed conglomerate of fetal abnormalities detected via ultrasonography, which was performed at 29.5 weeks of gestation. The patient presented with multiple abnormalities, which range from a suggested Arnold–Chiari malformation, compromising the lateral and third ventricles, liver calcifications, bilateral pyelocalic dilatations, other brain anomalies, and microcephaly. At 12 weeks of gestation, the vertical transmission of ZIKV was suspected. At 38.6 weeks of gestation, the newborn was delivered, with the weight in the 10th percentile (3,180 g), height in the 10th percentile (48 cm), and cephalic circumference under the 2nd percentile (31 cm). Due to the physical findings, brain magnetic resonance imaging (MRI) was performed, revealing a small and deviated brain stem, narrowing of the posterior fossa, a giant posterior fossa cyst with ventricular dilatation, a severe cortical and white matter thinning, cerebellar vermis with hypoplasia, and superior and lateral displacement of the cerebellum. In addition, hydrocephalus was displayed by the axial sequence, and the cerebral cortex was also compromised with lissencephaly. Schizencephaly was found with left frontal open-lip, and no intracranial calcifications were found. Two novel heterozygous nonsense mutations were identified using whole-exome sequencing, and both are located in exon 8 under the affection of ZIKV congenital syndrome (CZS) that produced a premature stop codon resulting in the truncation of the cyclin-dependent kinase 5 regulatory subunit-associated protein 2 (CDK5RAP2) protein.ConclusionWe used molecular and microbiological assessments to report the initial case of vertically transmitted ZIKV infection with congenital syndrome associated with a neurological syndrome, where a mutation in the CDK5RAP2 gene was also identified. The CDK5RAP2 gene encodes a pericentriolar protein that intervenes in microtubule nucleation and centriole attachment. Diallelic mutation has previously been associated with primary microcephaly.https://www.frontiersin.org/articles/10.3389/fgene.2021.530028/fullColombiamicrocephalywhole-exome sequencingZika virusvertical transmissionbrain abnormalities |
| spellingShingle | Estephania Candelo Estephania Candelo Ana Maria Sanz Diana Ramirez-Montaño Lorena Diaz-Ordoñez Ana Maria Granados Fernando Rosso Julian Nevado Pablo Lapunzina Harry Pachajoa Harry Pachajoa A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation Frontiers in Genetics Colombia microcephaly whole-exome sequencing Zika virus vertical transmission brain abnormalities |
| title | A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation |
| title_full | A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation |
| title_fullStr | A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation |
| title_full_unstemmed | A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation |
| title_short | A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation |
| title_sort | possible association between zika virus infection and cdk5rap2 mutation |
| topic | Colombia microcephaly whole-exome sequencing Zika virus vertical transmission brain abnormalities |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2021.530028/full |
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