Dravet syndrome is an archetypal rare severe epilepsy, considered "monogenic", typically caused by loss-of-function SCN1A variants. Despite a recognisable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. P
Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition / Helena Martins Custodio , Lisa M Clayton , Ravishankara Bellampalli, Susanna Pagni, Katri Silvennoinen, Richard Caswell ; Genomics England Research Consortium; Andreas Brunklaus , Renzo Guerrini , Bobby P C Koeleman , Johannes R Lemke , Rikke S Møller , Ingrid E Scheffer, Sarah Weckhuysen , Federico Zara , Sameer Zuberi , Karoline Kuchenbaecker , Simona Balestrini , James D Mills , Sanjay M Sisodiya. - In: BRAIN. - ISSN 1460-2156. - ELETTRONICO. - (2023), pp. 0-0. [10.1093/brain/awad111]
Widespread genomic influences on phenotype in Dravet syndrome, a 'monogenic' condition
Renzo Guerrini;Simona Balestrini;
2023
Abstract
Dravet syndrome is an archetypal rare severe epilepsy, considered "monogenic", typically caused by loss-of-function SCN1A variants. Despite a recognisable core phenotype, its marked phenotypic heterogeneity is incompletely explained by differences in the causal SCN1A variant or clinical factors. In 34 adults with SCN1A-related Dravet syndrome, we show additional genomic variation beyond SCN1A contributes to phenotype and its diversity, with an excess of rare variants in epilepsy-related genes as a set and examples of blended phenotypes, including one individual with an ultra-rare DEPDC5 variant and focal cortical dysplasia. P
I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
