Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy

Ivana A Souza; Maria A Gandini; Fang-Xiong Zhang; Wendy G Mitchell; Joyce Matsumoto; Jason Lerner; Tyler Mark Pierson; Gerald W Zamponi

doi:10.1186/s13041-019-0509-5

Pathogenic Cav3.2 channel mutation in a child with primary generalized epilepsy

Mol Brain. 2019 Oct 24;12(1):86. doi: 10.1186/s13041-019-0509-5.

Authors

Ivana A Souza¹, Maria A Gandini¹, Fang-Xiong Zhang¹, Wendy G Mitchell², Joyce Matsumoto³, Jason Lerner³, Tyler Mark Pierson^{4

5

6}, Gerald W Zamponi⁷

Affiliations

¹ Department of Physiology and Pharmacology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada.
² Neurology Division, Children's Hospital Los Angeles & Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles, USA.
³ Department of Pediatrics, Division of Pediatric Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
⁴ Department of Pediatrics, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁵ Department of Neurology, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁶ Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
⁷ Department of Physiology and Pharmacology, Alberta Children's Hospital Research Institute, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada. zamponi@ucalgary.ca.

Abstract

Two paternally-inherited missense variants in CACNA1H were identified and characterized in a 6-year-old child with generalized epilepsy. Febrile and unprovoked seizures were present in this child. Both variants were expressed in cis or isolation using human recombinant Cav3.2 calcium channels in tsA-201 cells. Whole-cell patch-clamp recordings indicated that one variant (c.3844C > T; p.R1282W) caused a significant increase in current density consistent with a pathogenic gain-of-function phenotype; while the other cis-related variant (c.5294C > T; p.A1765V) had a benign profile.

Keywords: Cav3.2; Epilepsy; Mutation; Seizure; T-type.

Publication types

Case Reports
Research Support, Non-U.S. Gov't

MeSH terms

Biophysical Phenomena
Calcium Channels, T-Type / genetics*
Child
Epilepsy, Generalized / genetics*
Female
Humans
Infant
Infant, Newborn
Mutation / genetics*

Substances

CACNA1H protein, human
Calcium Channels, T-Type

Supplementary concepts

Epilepsy, Idiopathic Generalized

Grants and funding

CIHR/Canada