SCN1A variants associated with sudden infant death syndrome

Catherine A Brownstein; Richard D Goldstein; Christopher H Thompson; Robin L Haynes; Emma Giles; Beth Sheidley; Matthew Bainbridge; Elisabeth A Haas; Othon J Mena; Jonathan Lucas; Bethann Schaber; Ingrid A Holm; Alfred L George; Hannah C Kinney; Annapurna H Poduri

doi:10.1111/epi.14055

SCN1A variants associated with sudden infant death syndrome

Epilepsia. 2018 Apr;59(4):e56-e62. doi: 10.1111/epi.14055. Epub 2018 Mar 30.

Authors

Catherine A Brownstein^{1

2

3}, Richard D Goldstein^{1

3

4}, Christopher H Thompson⁵, Robin L Haynes^{1

6}, Emma Giles^{1

6}, Beth Sheidley⁷, Matthew Bainbridge⁸, Elisabeth A Haas⁹, Othon J Mena¹⁰, Jonathan Lucas¹⁰, Bethann Schaber¹⁰, Ingrid A Holm^{1

2

3}, Alfred L George⁵, Hannah C Kinney^{1

3

6}, Annapurna H Poduri^{1

7

11

12}

Affiliations

¹ Robert's Program on Sudden Death in Pediatrics, Boston Children's Hospital, Boston, MA, USA.
² Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
³ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁴ Department of Medicine, Division of General Pediatrics, Boston Children's Hospital, Boston, MA, USA.
⁵ Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
⁶ Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.
⁷ Epilepsy Genetics Program, Department of Neurology, Boston Children's Hospital, Boston, MA, USA.
⁸ The Genomics Institute, Rady Children's Hospital, San Diego, CA, USA.
⁹ Department of Pathology, Rady Children's Hospital-San Diego, San Diego, CA, USA.
¹⁰ Office of the Medical Examiner, County of San Diego Medical Examiner's Office, San Diego, CA, USA.
¹¹ Department of Neurology, F. M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
¹² Department of Neurology, Harvard Medical School, Boston, MA, USA.

Abstract

We identified SCN1A variants in 2 infants who died of sudden infant death syndrome (SIDS) with hippocampal abnormalities from an exome sequencing study of 10 cases of SIDS but no history of seizures. One harbored SCN1A G682V, and the other had 2 SCN1A variants in cis: L1296M and E1308D, a variant previously associated with epilepsy. Functional evaluation in a heterologous expression system demonstrated partial loss of function for both G682V and the compound variant L1296M/E1308D. Our cases represent a novel association between SCN1A and SIDS, extending the SCN1A spectrum from epilepsy to SIDS. Our findings provide insights into SIDS and support genetic evaluation focused on epilepsy genes in SIDS.

Keywords: dentate gyrus; epilepsy; hippocampus; sodium channel; sudden unexpected death.

Publication types

Case Reports
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Female
Genetic Variation / genetics*
Humans
Infant
NAV1.1 Voltage-Gated Sodium Channel / genetics*
Sudden Infant Death / diagnosis*
Sudden Infant Death / genetics*

Substances

NAV1.1 Voltage-Gated Sodium Channel
SCN1A protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding