Sekwencjonowanie całego eksomu w opornej na leki epilepsji u dzieci: wydajność diagnostyczna i znaczenie kliniczne w warunkach ograniczonych zasobów
Whole-exome sequencing in pediatric drug-resistant epilepsy: diagnostic yield and clinical impact in a resource-limited setting
W skrócie
Badania przeprowadzone w Indonezji wykazały, że zaawansowana analiza genetyczna (sekwencjonowanie całego eksomu) może zidentyfikować przyczynę epilepsji opornej na leki u części dzieci. U 3 z 10 pacjentów znaleziono zmiany genetyczne odpowiadające za chorobę, co pozwoliło na bardziej spersonalizowane leczenie i doradztwo genetyczne dla rodzin. To badanie pokazuje, że test genetyczny jest ważnym narzędziem pomocnym w diagnozowaniu epilepsji, szczególnie w krajach o ograniczonych możliwościach dostępu do zaawansowanych badań medycznych.
Oryginalny abstract (angielski)
Drug-resistant epilepsy (DRE) in children is linked to poor developmental outcomes and increased mortality. Genetic factors are increasingly recognized in its pathogenesis, and whole- exome sequencing (WES) offers a promising diagnostic tool for early intervention, especially in cases with unclear etiology. However, data on the genetic causes of pediatric DRE remain scarce in Indonesia, a low-resource setting with limited access to advanced genetic testing. We conducted a retrospective review at the Neuropediatric Clinic of Sardjito Hospital, Yogyakarta, Indonesia, from January to December 2024. Children aged 0-18 years at the time of epilepsy diagnosis or genetic testing were included. WES was performed for all patients, and in cases with positive findings, Sanger sequencing was used to confirm variants in parents and siblings. WES identified pathogenic or likely pathogenic variants in 3 of 10 patients, with one patient harboring three variants. In total, three pathogenic or likely pathogenic variants were identified in TSC2, CC2D2A, and WDFY3, and two variants of uncertain significance were identified in CC2D2A and ATP6V1A. Among the five variants, two were missense mutations, two were nonsense mutations, and one was a frameshift mutation. WES can yield a definitive genetic diagnosis in a subset of patients, enabling individualized management, facilitating genetic counseling, and reducing the need for further diagnostic investigations.