Open AccessA novel CACNA1A variant in a child with early stroke and intractable epilepsy
Author(s) -
Gudenkauf Franciska J.,
Azamian Mahshid S.,
Hunter Jill V.,
Nayak Anuranjita,
Lalani Seema R.
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1383
Subject(s) - epilepsy , exome sequencing , medicine , ataxia , phenotype , pediatrics , exome , stroke (engine) , channelopathy , genetic heterogeneity , mutation , bioinformatics , neuroscience , genetics , biology , psychiatry , gene , mechanical engineering , engineering
Background CACNA1A variants have been described in several disorders that encompass a wide range of neurologic phenotypes, including hemiplegic migraine, ataxia, cognitive delay, and epilepsy. To date, ischemic stroke caused by a CACNA1A variant has only been reported once in the literature. Methods We describe a 4‐year‐old female with recurrent ischemic strokes beginning at 6 weeks of age, intractable epilepsy, and significant global developmental delay. Exome sequencing (ES) was completed for her evaluation. Results We found a novel de novo, likely pathogenic variant, p.Leu1692Gln in CACNA1A by ES. The substitution affects a leucine residue that is highly conserved in species from fish to primates. Conclusion We present the second case of recurrent ischemic strokes in a patient with CACNA1A mutation. Our findings expand the phenotypic heterogeneity related to Ca v 2.1 (P/Q ‐ type) calcium channel dysfunction and suggest consideration of CACNA1A disorder in evaluation of pediatric strokes.