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Genes & Development May 2017The re-emergence of Zika virus (ZIKV), a mosquito-borne and sexually transmitted flavivirus circulating in >70 countries and territories, poses a significant global... (Review)
Review
The re-emergence of Zika virus (ZIKV), a mosquito-borne and sexually transmitted flavivirus circulating in >70 countries and territories, poses a significant global threat to public health due to its ability to cause severe developmental defects in the human brain, such as microcephaly. Since the World Health Organization declared the ZIKV outbreak a Public Health Emergency of International Concern, remarkable progress has been made to gain insight into cellular targets, pathogenesis, and underlying biological mechanisms of ZIKV infection. Here we review the current knowledge and progress in understanding the impact of ZIKV exposure on the mammalian brain development and discuss potential underlying mechanisms.
Topics: Animals; Disease Outbreaks; Humans; Microcephaly; Zika Virus; Zika Virus Infection
PubMed: 28566536
DOI: 10.1101/gad.298216.117 -
Zhonghua Fu Chan Ke Za Zhi Mar 2023To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. A total of 9...
To explore the diagnostic value of chromosome karyotype analysis, chromosomal microarray analysis (CMA) and whole exome sequencing (WES) in microcephaly. A total of 9 cases of microcephaly fetuses diagnosed by prenatal ultrasound or children with microcephaly diagnosed after birth were selected from the Sixth Affiliated Hospital of Guangzhou Medical University from January 2014 to August 2022.Karyotype analysis and/or CMA were used to detect. The cases with negative karyotype analysis and CMA results were further sequenced by trio-based WES (Trio-WES). Then the coding genes contained in the pathogenic copy number variation (CNV) fragments were analyzed by gene ontology (GO) enrichment. The genes related to the development of the central nervous system contained in the pathogenic CNV and the pathogenic genes found by Trio-WES were combined for gene interaction network analysis. In this study, 9 cases of microcephaly were recruited, with the time of diagnosis ranged from 23 weeks of gestation to 7 years after birth, and the head circumference of fetus or children ranged from 18.3 to 42.5 cm (-7SD to -2SD). Karyotype analysis was detected in all 9 cases and no abnormality result was found. Eight cases were detected by CMA, and one abnormal was found. Five cases were detected by Trio-WES, and two cases were detected with likely pathogenic genes. The GO enrichment analysis of the coding gene in the 4p16.3 microdeletion (pathogenic CNV) region showed that: in biological process, it was mainly concentrated in phototransduction, visible light; in terms of molecular function, it was mainly concentrated in fibroblast growth factor binding; in terms of cell components, it was mainly concentrated in rough endoplasmic reticulum. Gene interaction network analysis suggested that CDC42 gene could interact with CTBP1, HTT and ASPM gene. CMA could be used as a first-line detection technique for microcephaly. When the results of chromosome karyotype analysis and/or CMA are negative, Trio-WES could improve the detection rate of pathogenicity of microcephaly.
Topics: Female; Humans; Pregnancy; DNA Copy Number Variations; Fetus; Karyotype; Karyotyping; Microarray Analysis; Microcephaly; Prenatal Diagnosis; Infant, Newborn
PubMed: 36935194
DOI: 10.3760/cma.j.cn112141-20221102-00675 -
The Lancet. Infectious Diseases Jan 2018Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection... (Review)
Review
Microcephaly is an important sign of neurological malformation and a predictor of future disability. The 2015-16 outbreak of Zika virus and congenital Zika infection brought the world's attention to links between Zika infection and microcephaly. However, Zika virus is only one of the infectious causes of microcephaly and, although the contexts in which they occur vary greatly, all are of concern. In this Review, we summarise important aspects of major congenital infections that can cause microcephaly, and describe the epidemiology, transmission, clinical features, pathogenesis, management, and long-term consequences of these infections. We include infections that cause substantial impairment: cytomegalovirus, herpes simplex virus, rubella virus, Toxoplasma gondii, and Zika virus. We highlight potential issues with classification of microcephaly and show how some infants affected by congenital infection might be missed or incorrectly diagnosed. Although Zika virus has brought the attention of the world to the problem of microcephaly, prevention of all infectious causes of microcephaly and appropriately managing its consequences remain important global public health priorities.
Topics: Central Nervous System Infections; Disease Management; Humans; Microcephaly
PubMed: 28844634
DOI: 10.1016/S1473-3099(17)30398-5 -
Disease Models & Mechanisms Jul 2023An outbreak of births of microcephalic patients in Brazil motivated multiple studies on this incident. The data left no doubt that infection by Zika virus (ZIKV) was the... (Review)
Review
An outbreak of births of microcephalic patients in Brazil motivated multiple studies on this incident. The data left no doubt that infection by Zika virus (ZIKV) was the cause, and that this virus promotes reduction in neuron numbers and neuronal death. Analysis of patients' characteristics revealed additional aspects of the pathology alongside the decrease in neuronal number. Here, we review the data from human, molecular, cell and animal model studies attempting to build the natural history of ZIKV in the embryonic central nervous system (CNS). We discuss how identifying the timing of infection and the pathways through which ZIKV may infect and spread through the CNS can help explain the diversity of phenotypes found in congenital ZIKV syndrome (CZVS). We suggest that intraneuronal viral transport is the primary mechanism of ZIKV spread in the embryonic brain and is responsible for most cases of CZVS. According to this hypothesis, the viral transport through the blood-brain barrier and cerebrospinal fluid is responsible for more severe pathologies in which ZIKV-induced malformations occur along the entire anteroposterior CNS axis.
Topics: Animals; Humans; Zika Virus; Zika Virus Infection; Microcephaly; Central Nervous System; Blood-Brain Barrier; Brain
PubMed: 37458166
DOI: 10.1242/dmm.050005 -
Canadian Family Physician Medecin de... Aug 2015To provide an evidence-based update emphasizing the importance of measuring head circumference (HC) in infants, with a focus on microcephaly. (Review)
Review
OBJECTIVE
To provide an evidence-based update emphasizing the importance of measuring head circumference (HC) in infants, with a focus on microcephaly.
QUALITY OF EVIDENCE
PubMed and EMBASE (OvidSP) were searched. Search terms used were head circumference and infants and measurement; microcephaly and infants and measurement; idiopathic microcephaly and infants; and congenital microcephaly and infants. Most of the references for this review were published in 2000 or later. Most evidence is level II.
MAIN MESSAGE
Serial measurement of HC should be incorporated into routine well-child care. Measure the distance around the back of the child's head with a nonelastic tape measure held above the eyebrows and ears, and plot the measurement on an age- and sex-appropriate growth chart. Microcephaly is HC more than 2 SD below the mean. The most common disability associated with microcephaly is intellectual delay; other common concomitant conditions include epilepsy, cerebral palsy, language delay, strabismus, ophthalmologic disorders, and cardiac, renal, urinary tract, and skeletal anomalies. An interdisciplinary approach to microcephaly is warranted. Although there are no specific interventions to enhance brain growth, dietary or surgical interventions might be helpful in some cases. Infants with microcephaly who show developmental delays might benefit from early intervention programs or developmental physical and occupational therapy.
CONCLUSION
Early identification of HC concerns by family physicians can be a critical first step in identifying disorders such as microcephaly, leading to referral to pediatric specialists and, as needed, provision of family-centred early intervention services.
Topics: Cephalometry; Child Development; Developmental Disabilities; Evidence-Based Medicine; Growth Charts; Humans; Infant; Microcephaly; Physical Examination
PubMed: 26505062
DOI: No ID Found -
Jornal de Pediatria 2016This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases. (Review)
Review
OBJECTIVE
This study aimed to critically review the literature available regarding the Zika virus outbreak in Brazil and its possible association with microcephaly cases.
SOURCES
Experts from Instituto do Cérebro do Rio Grande do Sul performed a critical (nonsystematic) literature review regarding different aspects of the Zika virus outbreak in Brazil, such as transmission, epidemiology, diagnostic criteria, and its possible association with the increase of microcephaly reports. The PubMed search using the key word "Zika virus" in February 2016 yielded 151 articles. The manuscripts were reviewed, as well as all publications/guidelines from the Brazilian Ministry of Health, World Health Organization and Centers for Disease Control and Prevention (CDC - United States).
SUMMARY OF FINDINGS
Epidemiological data suggest a temporal association between the increased number of microcephaly notifications in Brazil and outbreak of Zika virus, primarily in the Brazil's Northeast. It has been previously documented that many different viruses might cause congenital acquired microcephaly. Still there is no consensus on the best curve to measure cephalic circumference, specifically in preterm neonates. Conflicting opinions regarding the diagnosis of microcephaly (below 2 or 3 standard deviations) that should be used for the notifications were also found in the literature.
CONCLUSION
The development of diagnostic techniques that confirm a cause-effect association and studies regarding the physiopathology of the central nervous system impairment should be prioritized. It is also necessary to strictly define the criteria for the diagnosis of microcephaly to identify cases that should undergo an etiological investigation.
Topics: Aedes; Animals; Brazil; Disease Outbreaks; Female; Humans; Infant, Newborn; Insect Vectors; Microcephaly; Pregnancy; Pregnancy Complications, Infectious; Zika Virus; Zika Virus Infection
PubMed: 27049675
DOI: 10.1016/j.jped.2016.02.009 -
Viruses May 2018The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal... (Review)
Review
The recent Zika virus (ZIKV) outbreak in the Americas surprised all of us because of its rapid spread and association with neurologic disorders including fetal microcephaly, brain and ocular anomalies, and Guillain⁻Barré syndrome. In response to this global health crisis, unprecedented and world-wide efforts are taking place to study the ZIKV-related human diseases. Much has been learned about this virus in the areas of epidemiology, genetic diversity, protein structures, and clinical manifestations, such as consequences of ZIKV infection on fetal brain development. However, progress on understanding the molecular mechanism underlying ZIKV-associated neurologic disorders remains elusive. To date, we still lack a good understanding of; (1) what virologic factors are involved in the ZIKV-associated human diseases; (2) which ZIKV protein(s) contributes to the enhanced viral pathogenicity; and (3) how do the newly adapted and pandemic ZIKV strains alter their interactions with the host cells leading to neurologic defects? The goal of this review is to explore the molecular insights into the ZIKV⁻host interactions with an emphasis on host cell receptor usage for viral entry, cell innate immunity to ZIKV, and the ability of ZIKV to subvert antiviral responses and to cause cytopathic effects. We hope this literature review will inspire additional molecular studies focusing on ZIKV⁻host Interactions.
Topics: Animals; Host-Pathogen Interactions; Humans; Immunity, Innate; Mice; Microcephaly; Nervous System Diseases; Virus Internalization; Zika Virus; Zika Virus Infection
PubMed: 29724036
DOI: 10.3390/v10050233 -
Congenital Anomalies Nov 2017Autosomal recessive primary microcephaly (MCPH) is a very rare neuro-developmental disease with brain size reduction. More than a dozen loci encoding proteins of diverse... (Review)
Review
Autosomal recessive primary microcephaly (MCPH) is a very rare neuro-developmental disease with brain size reduction. More than a dozen loci encoding proteins of diverse function have been shown to be responsible for MCPH1-13. Mutations in the D40/KNL1/CASC5 gene, which was initially characterized as a gene involved in chromosomal translocation in leukemia and as a member of the cancer/testis gene family, was later found to encode a kinetochore protein essential for mitotic cell division and to cause MCPH4. Although our previous studies showed that this gene is required for cell growth and division in vitro and in animal experiments, the revelation that mutations in this gene caused microcephaly provides in vivo evidence of a critical role in brain growth. In this review, we describe mutated gene targets responsible for MCPH1-13 and summarize clinical studies of, and molecular and biological aspects of the gene and encoded protein responsible for MCPH4.
Topics: Animals; Brain; Cell Cycle Proteins; Gene Expression; Humans; Kinetochores; Microcephaly; Microtubule-Associated Proteins; Microtubules; Mitosis; Mutation; Neurons; Protein Binding; Protein Domains; Protein Interaction Mapping
PubMed: 28901661
DOI: 10.1111/cga.12252 -
Cell Cycle (Georgetown, Tex.) Feb 2017
Topics: Animals; Biological Evolution; Humans; Intracellular Signaling Peptides and Proteins; Microcephaly; Microtubules; Models, Biological; Protein Serine-Threonine Kinases; Spindle Apparatus
PubMed: 27830983
DOI: 10.1080/15384101.2016.1252584 -
International Journal of Biological... 2023Loss of function in transport protein particles (TRAPP) links a new set of emerging genetic disorders called "TRAPPopathies". One such disorder is NIBP syndrome,...
Loss of function in transport protein particles (TRAPP) links a new set of emerging genetic disorders called "TRAPPopathies". One such disorder is NIBP syndrome, characterized by microcephaly and intellectual disability, and caused by mutations of , a crucial and unique member of TRAPPII. To investigate the neural cellular/molecular mechanisms underlying microcephaly, we developed Nibp/Trappc9-deficient animal models using different techniques, including morpholino knockdown and CRISPR/Cas mutation in zebrafish and Cre/LoxP-mediated gene targeting in mice. Nibp/Trappc9 deficiency impaired the stability of the TRAPPII complex at actin filaments and microtubules of neurites and growth cones. This deficiency also impaired elongation and branching of neuronal dendrites and axons, without significant effects on neurite initiation or neural cell number/types in embryonic and adult brains. The positive correlation of TRAPPII stability and neurite elongation/branching suggests a potential role for TRAPPII in regulating neurite morphology. These results provide novel genetic/molecular evidence to define patients with a type of non-syndromic autosomal recessive intellectual disability and highlight the importance of developing therapeutic approaches targeting the TRAPPII complex to cure TRAPPopathies.
Topics: Animals; Mice; Intellectual Disability; Microcephaly; Neurites; Neurons; Zebrafish
PubMed: 37416774
DOI: 10.7150/ijbs.78489