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Application of Genomics in Complex Disorders: Focus on Pharmacogenomics Informed Theraputics

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: 20 December 2024 | Viewed by 1281

Special Issue Editor


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Guest Editor
Section of Psychiatry, Departement of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy
Interests: precision medicine; risk prediction; copy number variation; polygenic risk score; omics

Special Issue Information

Dear Colleagues,

The field of genomics has seen unprecedented progresses in the development of novel experimental and analytical tools that are supporting the transition of clinical practice toward precision medicine. Data driven medical approaches are starting to see implementation in several areas including oncology, neurology, and to some extent, psychiatry. The use of omics technologies, integrated by digital monitoring data, electronic health records, and other omics technologies (metabolomics, proteomics, epigenomics) is increasing the accuracy of prediction for specific for complex traits. For instance, the analysis of genome-wide derived polygenic risk score integrated by cognitive data and brain imaging has reached adequate levels of accuracy for clinical implementation in neurodegenerative disorders. This special issue aims to collect novel research data and syntheses of the literature on the progresses of genomic research in complex disorders, focusing on the clinical relevance of risk prediction algorithms and data driven clinical decision making (i.e., pharmacogenomics informed theraputics).

Prof. Dr. Mirko Manchia
Guest Editor

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Published Papers (1 paper)

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21 pages, 4908 KiB  
Case Report
PLP1-Targeting Antisense Oligonucleotides Improve FOXG1 Syndrome Mice
by Daniel C. S. Tan, Seonghee Jung, Yuanyuan Deng, Nicolle Morey, Gabriella Chan, Andre Bongers, Yazi D. Ke, Lars M. Ittner and Fabien Delerue
Int. J. Mol. Sci. 2024, 25(19), 10846; https://doi.org/10.3390/ijms251910846 - 9 Oct 2024
Viewed by 764
Abstract
FOXG1 syndrome is a rare neurodevelopmental disorder of the telencephalon, for which there is no cure. Underlying heterozygous pathogenic variants in the Forkhead Box G1 (FOXG1) gene with resulting impaired or loss of FOXG1 function lead to severe neurological impairments. Here, [...] Read more.
FOXG1 syndrome is a rare neurodevelopmental disorder of the telencephalon, for which there is no cure. Underlying heterozygous pathogenic variants in the Forkhead Box G1 (FOXG1) gene with resulting impaired or loss of FOXG1 function lead to severe neurological impairments. Here, we report a patient with a de novo pathogenic single nucleotide deletion c.946del (p.Leu316Cysfs*10) of the FOXG1 gene that causes a premature protein truncation. To study this variant in vivo, we generated and characterized Foxg1 c946del mice that recapitulate hallmarks of the human disorder. Accordingly, heterozygous Foxg1 c946del mice display neurological symptoms with aberrant neuronal networks and increased seizure susceptibility. Gene expression profiling identified increased oligodendrocyte- and myelination-related gene clusters. Specifically, we showed that expression of the c946del mutant and of other pathogenic FOXG1 variants correlated with overexpression of proteolipid protein 1 (Plp1), a gene linked to white matter disorders. Postnatal administration of Plp1-targeting antisense oligonucleotides (ASOs) in Foxg1 c946del mice improved neurological deficits. Our data suggest Plp1 as a new target for therapeutic strategies mitigating disease phenotypes in FOXG1 syndrome patients. Full article
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