Naslov
Diagnostic exome sequencing of syndromic epilepsy patients in clinical practice

Autori
Tumienė, B. ; Maver, A. ; Writzl, K. ; Hodžić, A. ; Čuturilo, G. ; Kuzmanić-Šamija, R. ; Čulić, V. ; Peterlin, B.

Izvornik
Clinical Genetics (0009-9163) 93 (2018), 5; 1057-1062

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
diagnostic yield epilepsy genetics ; monogenic epilepsies ; next-generation sequencing ; SOX5 ; UBA5

Sažetak
Although genetic revolution of recent years has vastly expanded a list of genes implicated in epilepsies, complex architecture of epilepsy genetics is still largely unknown, consequently, universally accepted workflows for epilepsy genetic testing in a clinical practice are missing. We present a comprehensive NGS-based diagnostic approach addressing both the clinical and genetic heterogeneity of disorders involving epilepsy or seizures. A bioinformatic panel of 862 epilepsy- or seizure-associated genes was applied to Mendeliome (4813 genes) or whole-exome sequencing data as a first stage, while the second stage included untargeted variant interpretation. Eighty-six consecutive patients with epilepsy or seizures associated with neurodevelopmental disorders and/or congenital malformations were investigated. Of the 86 probands, 42 harbored pathogenic and likely pathogenic variants, giving a diagnostic yield of 49%. Two patients were diagnosed with pathogenic copy number variations and 2 had causative mitochondrial DNA variants. Eleven patients (13%) were diagnosed with diseases with specific treatments. Besides, genomic approach in diagnostics had multiple additional benefits due to mostly non-specific, overlapping, not full-blown phenotypes and abilities to diagnose novel and ultra rare epilepsy-associated diseases. Likely pathogenic variants were identified in SOX5 gene, not previously associated with epilepsy, and UBA5, a recently associated with epilepsy gene.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA