Two Novel Variants Affecting CDKL5 Transcript Associated with Epileptic Encephalopathy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F17%3A10373658" target="_blank" >RIV/00216208:11130/17:10373658 - isvavai.cz</a>
Alternative codes found
RIV/00064203:_____/17:10373658
Result on the web
<a href="https://doi.org/10.1089/gtmb.2017.0110" target="_blank" >https://doi.org/10.1089/gtmb.2017.0110</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1089/gtmb.2017.0110" target="_blank" >10.1089/gtmb.2017.0110</a>
Alternative languages
Result language
angličtina
Original language name
Two Novel Variants Affecting CDKL5 Transcript Associated with Epileptic Encephalopathy
Original language description
Background: Variants in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been reported as being etiologically associated with early infantile epileptic encephalopathy type 2 (EIEE2). We report on two patients, a boy and a girl, with EIEE2 that present with early onset epilepsy, hypotonia, severe intellectual disability, and poor eye contact. Methods: Massively parallel sequencing (MPS) of a custom-designed gene panel for epilepsy and epileptic encephalopathy containing 112 epilepsy-related genes was performed. Sanger sequencing was used to confirm the novel variants. For confirmation of the functional consequence of an intronic CDKL5 variant in patient 2, an RNA study was done. Results: DNA sequencing revealed de novo variants in CDKL5, a c.2578C>T (p. Gln860*) present in a hemizygous state in a 3-year-old boy, and a potential splice site variant c.463+5G>A in heterozygous state in a 5-year-old girl. Multiple in silico splicing algorithms predicted a highly reduced splice site score for c.463+5G>A. A subsequent mRNA study confirmed an aberrant shorter transcript lacking exon 7. Conclusions: Our data confirmed that variants in the CDKL5 are associated with EIEE2. There is credible evidence that the novel identified variants are pathogenic and, therefore, are likely the cause of the disease in the presented patients. In one of the patients a stop codon variant is predicted to produce a truncated protein, and in the other patient an intronic variant results in aberrant splicing.
Czech name
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Czech description
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Classification
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
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2017
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Genetic Testing and Molecular Biomarkers
ISSN
1945-0265
e-ISSN
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Volume of the periodical
21
Issue of the periodical within the volume
10
Country of publishing house
US - UNITED STATES
Number of pages
6
Pages from-to
613-618
UT code for WoS article
000413278200008
EID of the result in the Scopus database
2-s2.0-85032876418