Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May;59(5):3159-3169.
doi: 10.1007/s12035-022-02792-9. Epub 2022 Mar 12.

Distinct Epileptogenic Mechanisms Associated with Seizures in Wolf-Hirschhorn Syndrome

Thiago Corrêa  1   2 , Maytza Mayndra  3 , Cíntia B Santos-Rebouças  4
Affiliations

Distinct Epileptogenic Mechanisms Associated with Seizures in Wolf-Hirschhorn Syndrome

Thiago Corrêa et al. Mol Neurobiol. 2022 May.

Abstract

Seizures are one of the clinical hallmarks of Wolf-Hirschhorn syndrome (WHS), causing a significant impact on the life quality, still in the first years of life. Even that the knowledge about WHS-related seizure candidate genes has grown, cumulative evidence suggests synergic haploinsufficiency of distinct genes within cellular networks that should be better elucidated. Herein, we evaluated common mechanisms between candidate genes from WHS seizure-susceptibility regions (SSR) and genes globally associated with epilepsy. For this purpose, data from 94 WHS patients delineated by chromosomal microarray analysis were integrated into a tissue-specific gene network with gene expression, drugs, and biological processes. We found functional modules and signaling pathways involving candidate and new genes with potential involvement in the WHS-related seizure phenotype. The proximity among the previous reported haploinsufficient candidate genes (PIGG, CPLX1, CTBP1, LETM1) and disease genes associated with epilepsy suggests not just one, but different impaired mechanisms in cellular networks responsible for the balance of neuronal activity in WHS patients, from which neuron communication is the most impaired in WHS-related seizures. Furthermore, CTBP1 obtained the largest number of drug associations, reinforcing its importance for adaptations of brain circuits and its putative use as a pharmacological target for treating seizures/epilepsy in patients with WHS.

Keywords: CPLX1; CTBP1; LETM1; PIGG; Seizures; Wolf-Hirschhorn syndrome.

PubMed Disclaimer

References

    1. Maas NMC, Van Buggenhout G, Hannes F et al (2008) Genotype-phenotype correlation in 21 patients with Wolf-Hirschhorn syndrome using high resolution array comparative genome hybridisation (CGH). J Med Genet 45:71–80. https://doi.org/10.1136/jmg.2007.052910 - DOI - PubMed
    1. Zollino M, Murdolo M, Marangi G et al (2008) On the nosology and pathogenesis of Wolf-Hirschhorn syndrome: genotype-phenotype correlation analysis of 80 patients and literature review. Am J Med Genet Part C Semin Med Genet 148:257–269. https://doi.org/10.1002/ajmg.c.30190 - DOI
    1. South ST, Hannes F, Fisch GS et al (2008) Pathogenic significance of deletions distal to the currently described Wolf-Hirschhorn syndrome critical regions on 4p16.3. Am J Med Genet Part C Semin Med Genet 148:270–274. https://doi.org/10.1002/ajmg.c.30188 - DOI
    1. Battaglia A, Carey JC, South ST (2015) Wolf-Hirschhorn syndrome: a review and update. Am J Med Genet Part C Semin Med Genet 169:216–223. https://doi.org/10.1002/ajmg.c.31449 - DOI - PubMed
    1. Corrêa T, Mergener R, Leite JCL et al (2018) Cytogenomic integrative network analysis of the critical region associated with Wolf-Hirschhorn syndrome. Biomed Res Int 2018. https://doi.org/10.1155/2018/5436187