Clinical Genetic Characteristics of Epilepsy Due to Mutations in the PCDH19 Gene (OMIM: 300088)
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Clinical Genetic Characteristics of Epilepsy Due to Mutations in the PCDH19 Gene (OMIM: 300088) E. L. Dadali,1,2 I. A. Mishina,1 A. O. Borovikov,1 A. A. Sharkov,2 and I. V. Kanivets3
Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 120, No. 1, Iss. 1, pp. 55–61, January, 2020. Original article submitted September 13, 2019. Accepted September 23, 2019. Objectives: to analyze the clinical genetic characteristics of PCDH19-associated epilepsy in a cohort of patients from the population of the Russian Federation. Materials and methods. The cohort of patients with early epileptic encephalopathy consisted of 16 patients aged from 10 months to 30 years. All patients underwent neurological examination by standard methods, exome sequencing, and electroencephalogram monitoring. Results. Most of the mutations detected were frameshift mutations or mutations forming a stop codon. Six were duplications and four were deletions of a single nucleotide, while three were nonsense mutations. Polymorphism in the clinical manifestations of convulsions were found, which were independent of the type of mutation and its location, which is consistent with results reported by other authors. Conclusions. This study of the clinical genetic features of our patients leads to the conclusion that the PCDH19 gene has so-called hot spots, which are mutated more frequently than other parts of the gene, and that the clinical picture of epileptic encephalopathy type 9, induced by mutations in the PCDH19 gene, is variable. Keywords: early epileptic encephalopathy, PCDH19, convulsions, developmental delay.
gave birth to afflicted daughters, while all sons were healthy [6]. However, mapping and identification of the PCDH19 gene, mutations in which lead to the disease, were carried out by Wolverton only in 2001 [7]. The gene is located in chromosome Xq22.1 and consists of six coding exons. The structure and functions of the protein product of the gene have been quite well studied. It has been shown to belong to the protocadherin subfamily – these are calcium-dependent proteases involved in cell adhesion and have an important role in neuron migration process and synapse formation in structures of the cerebral cortex during the embryonic period [8–10]. Protocadherin type 19 consists of three segments: the extracellular, the transmembrane, and the intracellular segments. The main role in the functioning of this protein is played by the extracellular segment, which consists of six functional domains. A total of 229 mutations and 14 large chromosomal rearrangements in the area of the PCDH19 gene have now been identified. Most of the mutations in patients with PCDH19-associated epilepsy are found in the first exon of the PCDH19 gene, encoding the extracellular and transmembrane domains and part of the intracellular domain of the protein [10].
Monogenic variants of early infantile epileptic encephalopathy (EIEE) constitute a heterogeneous group of diseases characterized by drug-refractory convulsions manifest in early childhood with
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