RT Journal Article
T1 A de novo heterozygous missense BSCL2 variant in 2 siblings with intractable developmental and epileptic encephalopathy
A1 Sánchez Iglesias, Sofía
A1 Jou, Cristina
A1 Araujo-Vilar, David
A1 Fernández Marmiesse, Ana
A1 Darling, Alejandra
A1 O'Callaghan, Mar
A1 Tonda, Raul
K1 Whole exome sequencing
K1 BSCL2
K1 Seipin
K1 Early infantile epileptic encephalopathy
AB Purpose: We present the case of 2 siblings with profound refractory epilepsy and neurological regression that began at the ages of 3 and 6 months. Diagnosis remained elusive despite extensive metabolic and genetic workups, including use of a targeted next-generation sequencing panel for epilepsy genes.Methods: Whole-exome sequencing was performed for the 2 siblings and their unaffected parents, in addition to fibroblast cell culture, RNA extraction and reverse-transcription, and cDNA PCR. Brain tissue from one of the siblings was collected post-mortem for neuropathological examination, including histology and immunohistochemistry. Results: Ade novo nucleotide change (c.566 T > A; p.(Met189Lys)) in exon 4 of the BSCL2 gene was detected in the 2 siblings, and confirmed by Sanger sequencing. This variant was absent in the parents and in a third, unaffected sibling.Conclusion: Given thede novo nature of the variant, its absence from public and in-house databases, our in silico pathogenicity predictions, and co-segregation of the variant with the disease phenotype, we believe that this novel variant is associated with the epileptic encephalopathy phenotype of the 2 siblings. Our findings provide the first evidence of an association between a heterozygous BSCL2 variant and developmental and early infantileepileptic encephalopathy. Further functional studies will be needed to elucidate the pathophysiological mechanisms underlying this new BSCL2-associated phenotype.
PB Seizure-European Journal of Epilepsy
YR 2019
FD 2019
LK http://hdl.handle.net/10347/32027
UL http://hdl.handle.net/10347/32027
LA eng
NO Ana Fernández-Marmiesse, Sofía Sánchez-Iglesias, Alejandra Darling, María M. O'Callaghan, Raúl Tonda, Cristina Jou, David Araújo-Vilar, A de novo heterozygous missense BSCL2 variant in 2 siblings with intractable developmental and epileptic encephalopathy, Seizure, Volume 71, 2019, Pages 161-165, ISSN 1059-1311, https://doi.org/10.1016/j.seizure.2019.07.019.
NO This research was partially funded by the Consellería de Industria,Xunta de Galicia (grant number ED341b 2017/19), and by FundaciónMutua Madrileña (Call 2015). S.S-I is a recipient of a Research Fellowship from the Asociación Española de Familiares y Afectados deLipodistrofias (AELIP).
DS Minerva
RD 23 abr 2026