Clinical and genetic characteristics of patients with type 2 early infantile epileptic encephalopathy caused by CDKL5 gene mutations

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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.

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;

Email: fake@neicon.ru
ORCID iD: 0000-0001-5602-2805
1 Moskvorechye St., Moscow 115522, Russia;
1 Ostrovityanova St., Moscow 117997, Russia; Russian Federation

I. A. Akimova

Medical Genetic Research Center named after acad. N.P. Bochkov;
1 Moskvorechye St., Moscow 115522, Russia;

Author for correspondence.
Email: akimova@med-gen.ru
ORCID iD: 0000-0002-9092-6581

Medical Genetic Research Center named after acad. N.P. Bochkov;
1 Moskvorechye St., Moscow 115522, Russia;

Russian Federation

F. A. Konovalov

Genomed LLC;

Email: fake@neicon.ru
8/5 Podolskoe Shosse, Moscow 115093, Russia; Russian Federation

P. A. Shatalov

Genotek LLC;

Email: fake@neicon.ru
17/1 Nastavnicheskiy Per., Moscow 105120, Russia Russian Federation

A. Yu. Krasnenko

Genotek LLC;

Email: fake@neicon.ru
17/1 Nastavnicheskiy Per., Moscow 105120, Russia Russian Federation

V. V. Strelnikov

Medical Genetic Research Center named after acad. N.P. Bochkov;

Email: fake@neicon.ru
1 Moskvorechye St., Moscow 115522, Russia; Russian Federation

M. A. Ampleeva

Genomed LLC;

Email: fake@neicon.ru
ORCID iD: 0000-0003-2185-4753
8/5 Podolskoe Shosse, Moscow 115093, Russia; Russian Federation

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