Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations
E. L. Dadali,
I. A. Akimova,
F. A. Konovalov,
P. A. Shatalov,
A. Yu. Krasnenko,
V. V. Strelnikov,
M. A. Ampleeva https://doi.org/10.17650/2073-8803-2019-14-3-28-36
Abstract
Early infantile epileptic encephalopathies (EIEE) are a group of disorders characterized by pharmacoresistant epileptic seizures manifesting in infancy and leading to psychomotor retardation. The most common genetic variant with X-linked dominant inheritance is type 2 EIEE associated with CDKL5 gene mutations.
We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE.
The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.
We evaluated the prevalence of this type of EIEE among Russian patients (n = 148) with epileptic seizures manifesting in infancy and analyzed their clinical and genetic characteristics. We performed exome sequencing for all patients; 15 (10 %) of them (aged between 2 months and 5 years) were found to have CDKL5 gene mutations and were, therefore, diagnosed with type 2 EIEE.
The results of correlation analysis suggest that the severity of clinical manifestations of type 2 EIEE is largely determined by the location of mutations affecting the function of the protein encoded by this gene. This is important to ensure better understanding of type 2 EIEE etiology and predict it severity in patients with different allelic variants.
Supporting agencies: The study was performed as part of the state task of the Ministry of Education and Science of Russia to carry out research work in 2019
About the Authors
E. L. Dadali
Medical Genetic Research Center named after acad. N.P. Bochkov;
N.I. Pirogov Russian National Research Medical University, Ministry of Health of Russia;
Russian Federation
1 Moskvorechye St., Moscow 115522, Russia;
1 Ostrovityanova St., Moscow 117997, Russia;
Russian Federation
1 Moskvorechye St., Moscow 115522, Russia;
1 Ostrovityanova St., Moscow 117997, Russia;
I. A. Akimova
Medical Genetic Research Center named after acad. N.P. Bochkov;
1 Moskvorechye St., Moscow 115522, Russia;
Russian Federation
Russian Federation
Medical Genetic Research Center named after acad. N.P. Bochkov;
1 Moskvorechye St., Moscow 115522, Russia;
F. A. Konovalov
Genomed LLC;
Russian Federation
8/5 Podolskoe Shosse, Moscow 115093, Russia;
Russian Federation
8/5 Podolskoe Shosse, Moscow 115093, Russia;
P. A. Shatalov
Genotek LLC;
Russian Federation
17/1 Nastavnicheskiy Per., Moscow 105120, Russia
Russian Federation
17/1 Nastavnicheskiy Per., Moscow 105120, Russia
A. Yu. Krasnenko
Genotek LLC;
Russian Federation
17/1 Nastavnicheskiy Per., Moscow 105120, Russia
Russian Federation
17/1 Nastavnicheskiy Per., Moscow 105120, Russia
V. V. Strelnikov
Medical Genetic Research Center named after acad. N.P. Bochkov;
Russian Federation
1 Moskvorechye St., Moscow 115522, Russia;
Russian Federation
1 Moskvorechye St., Moscow 115522, Russia;
M. A. Ampleeva
Genomed LLC;
Russian Federation
8/5 Podolskoe Shosse, Moscow 115093, Russia;
Russian Federation
8/5 Podolskoe Shosse, Moscow 115093, Russia;
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Review
For citations:
Dadali E.L., Akimova I.A., Konovalov F.A., Shatalov P.A., Krasnenko A.Yu., Strelnikov V.V., Ampleeva M.A. Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations. Russian Journal of Child Neurology. 2019;14(3):28-36. (In Russ.) https://doi.org/10.17650/2073-8803-2019-14-3-28-36
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