Mutation in PHACTR1 associated with multifocal epilepsy with infantile spasms and hypsarrhythmia

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F21%3A00555396" target="_blank" >RIV/68378050:_____/21:00555396 - isvavai.cz</a>
Result on the web
<a href="https://onlinelibrary.wiley.com/doi/10.1111/cge.13926" target="_blank" >https://onlinelibrary.wiley.com/doi/10.1111/cge.13926</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1111/cge.13926" target="_blank" >10.1111/cge.13926</a>

Result language
angličtina
Original language name
Mutation in PHACTR1 associated with multifocal epilepsy with infantile spasms and hypsarrhythmia
Original language description
A young boy with multifocal epilepsy with infantile spasms and hypsarrhythmia with minimal organic lesions of brain structures underwent DNA diagnosis using whole-exome sequencing. A heterozygous amino-acid substitution p.L519R in a PHACTR1 gene was identified. PHACTR1 belongs to a protein family of G-actin binding protein phosphatase 1 (PP1) cofactors and was not previously associated with a human disease. The missense single nucleotide variant in the proband was shown to occur de novo in the paternal allele. The mutation was shown in vitro to reduce the affinity of PHACTR1 for G-actin, and to increase its propensity to form complexes with the catalytic subunit of PP1. These properties are associated with altered subcellular localization of PHACTR1 and increased ability to induce cytoskeletal rearrangements. Although the molecular role of the PHACTR1 in neuronal excitability and differentiation remains to be defined, PHACTR1 has been previously shown to be involved in Slack channelopathy pathogenesis, consistent with our findings. We conclude that this activating mutation in PHACTR1 causes a severe type of sporadic multifocal epilepsy in the patient.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10603 - Genetics and heredity (medical genetics to be 3)

Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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