Abstrakt
Epilepsy is heterogeneous chronic neurological disorder with prevalence 8/1000. Copy number variants (CNVs) are responsible for 2-11 % of epilepsies.
We present a cohort of 193 patients with epilepsy, both children and adults, divided in two groups - 49 patients with isolated epilepsy and 144 patients with syndromic epilepsy (i.e. associated with developmental delay, dysmorphic features etc). ArrayCGH platform SurePrint G3 ISCA 4x180 and 8x60 (Agilent Technologies) were used for the examinations.
We detected CNVs in 32/193 of patients (16.6 %): 16 deletions (50 %), 12 duplications (38 %), one triplication (3 %) and more than one CNV were detected in three patients (9 %). 15 CNVs were pathogenic and explaining the phenotype, three CNVs were probably pathogenic, two were benign and 12 were variants of unknown significance (VOUS). Pathogenic and probably pathogenic CNVs were detected only in syndromic patients.
In patients with isolated epilepsy only VOUS and benign variants were detected. Origin of variants was determined as maternal (20 %), paternal (13 %), de novo (30 %) and was unknown in 37 % of cases.
CNVs size ranged from 15 kb to 9 Mb. Except of CNVs located in regions associated with known syndromes and epilepsy "hotspots", we detected new non-recurrent CNVs.
Using arrayCGH, we identified CNVs as a cause of epilepsy in 18/144 syndromic patients (12.5 %). CNVs play an important role in aetiology of epilepsies.
Therefore arrayCGH should be included into diagnostic algorithm as a first-choice genetic method in patients with syndromic epilepsy.