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2023

ANUÁRIO DO HOSPITAL
DONA ESTEFÂNIA

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DIAGNOSTIC TARGETED RESEQUENCING IN 349 PATIENTS WITH DRUG-RESISTANT PEDIATRIC EPILEPSIES IDENTIFIES CAUSATIVE MUTATIONS IN 30 DIFFERENT GENES

Elena Parrini1, Carla Marini1, Davide Mei1, Anna Galuppi1, Elena Cellini1, Daniela Pucatti1, Laura Chiti1, Domenico Rutigliano1, Claudia Bianchini1, Simona Virdò1, Dalila De Vita1, Stefania Bigoni2, Carmen Barba1, Francesco Mari1, Martino Montomoli1, Tiziana Pisano1, Anna Rosati1, Clinical Study Group (including Sandra Jacinto)3 and Renzo Guerrini1

1- Pediatric Neurology, Neurogenetics and Neurobiology Unit and Laboratories, Neuroscience Department, A Meyer Children’s Hospital, University of Florence, Florence, Italy
2- UOL of Medical Genetics, Ferrara University Hospital, Ferrara, Italy
3- Pediatric Neurology Department, Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal

Human Mutation 2017 Feb; 38(2):216-225. Epub 2016 Dec 9 (publicação)

Targeted resequencing gene panels are used in the diagnostic setting to identify gene defects in epilepsy. We performed targeted resequencing using a 30-genes panel and a 95-genes panel in 349 patients with drug-resistant epilepsies beginning in the first years of life. We identified 71 pathogenic variants, 42 of which novel, in 30 genes, corresponding to 20.3% of the probands. In 66% of mutation positive patients, epilepsy onset occurred before the age of 6 months. The 95-genes panel allowed a genetic diagnosis in 22 (6.3%) patients that would have otherwise been missed using the 30-gene panel. About 50% of mutations were identified in genes coding for sodium and potassium channel components. SCN2A was the most frequently mutated gene followed by SCN1A, KCNQ2, STXBP1, SCN8A, CDKL5, and MECP2. Twenty-nine mutations were identified in 23 additional genes, most of them recently associated with epilepsy. Our data show that panels targeting about 100 genes represent the best cost-effective diagnostic option in pediatric drug-resistant epilepsies. They enable molecular diagnosis of atypical phenotypes, allowing tobroaden phenotype-genotype correlations. Molecular diagnosis might influence patients' management and translate into better and specific treatment recommendations in some conditions.

Palavras Chave: Drug-resistant pediatric epilepsy, targeted resequencing