A de novo heterozygous missense BSCL2 variant in 2 siblings with intractable developmental and epileptic encephalopathy.
Seizure
; 71: 161-165, 2019 Oct.
Article
in En
| MEDLINE
| ID: mdl-31369919
ABSTRACT
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 infantile epileptic encephalopathy. Further functional studies will be needed to elucidate the pathophysiological mechanisms underlying this new BSCL2-associated phenotype.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spasms, Infantile
/
GTP-Binding Protein gamma Subunits
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Drug Resistant Epilepsy
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Child
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Seizure
Journal subject:
NEUROLOGIA
Year:
2019
Document type:
Article
Affiliation country: