A Possible Association Between Zika Virus Infection and CDK5RAP2 Mutation

Area of Science:

• Virology
• Genetics
• Neurology
• Obstetrics

Background:

• Zika virus (ZIKV), a Flaviviridae family member, is transmitted by Aedes mosquitoes.
• ZIKV emerged in Brazil in 2014, causing an epidemic linked to microcephaly cases.
• Vertical transmission of ZIKV can lead to congenital Zika syndrome (CZS).

Purpose of the Study:

• To report a case of vertically transmitted ZIKV infection with severe congenital abnormalities.
• To investigate the genetic basis of neurological complications in a newborn exposed to ZIKV in utero.
• To highlight the association between ZIKV infection, a specific gene mutation, and neurological deficits.

Main Methods:

• Clinical case report of a pregnant woman with suspected ZIKV exposure and fetal abnormalities.
• Ultrasonography and Magnetic Resonance Imaging (MRI) to assess fetal and neonatal brain development.
• Whole-exome sequencing to identify genetic mutations associated with observed abnormalities.

Main Results:

• A newborn presented with microcephaly and severe brain malformations, including Arnold-Chiari malformation, hydrocephalus, lissencephaly, and schizencephaly.
• Whole-exome sequencing revealed two novel heterozygous nonsense mutations in the CDK5RAP2 gene.
• These mutations resulted in a truncated CDK5RAP2 protein, implicated in microtubule nucleation and centriole attachment.

Conclusions:

• This case represents the first documented instance of vertically transmitted ZIKV infection causing congenital and neurological syndromes.
• A mutation in the CDK5RAP2 gene is identified as a potential contributing factor to the observed microcephaly and brain anomalies.
• The findings underscore the severe teratogenic potential of ZIKV and highlight the role of CDK5RAP2 in neurodevelopment.