Neuropediatrics 2018; 49(01): 059-062
DOI: 10.1055/s-0037-1606370
Short Communication
Georg Thieme Verlag KG Stuttgart · New York

Biallelic Mutations in SLC1A2; an Additional Mode of Inheritance for SLC1A2-Related Epilepsy

Matias Wagner*
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
2   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
3   Institut für Neurogenomik, Helmholtz Zentrum München, Neuherberg, Germany
,
Mirjana Gusic*
2   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
,
Roman Günthner
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
4   Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany
,
Bader Alhaddad
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
,
Reka Kovacs-Nagy
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
,
Christine Makowski
5   Department of Pediatrics, Technische Universität München, Munich, Germany
,
Friedrich Baumeister
6   Children's Hospital, RoMed Klinikum, Rosenheim, Germany
,
Tim Strom
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
2   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
,
Thomas Meitinger
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
2   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
,
Holger Prokisch*
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
2   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
,
Saskia B. Wortmann*
1   Institute of Human Genetics, Technische Universität München, Munich, Germany
2   Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
7   Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University, Salzburg, Austria
› Author Affiliations
Further Information

Publication History

26 April 2017

20 July 2017

Publication Date:
15 September 2017 (online)

Abstract

Recently, heterozygous de novo mutations in SCL1A2 have been reported to underlie severe early-onset epileptic encephalopathy. In one male presenting with epileptic seizures and visual impairment, we identified a novel homozygous splicing variant in SCL1A2 (c.1421 + 1G > C) by using exome sequencing. Functional studies on cDNA level confirmed a consecutive loss of function. Our findings suggest that not only de novo mutations but also biallelic variants in SLC1A2 can cause epilepsy and that there is an additional autosomal recessive mode of inheritance. These findings also contribute to the understanding of the genetic mechanism of autosomal dominant SLC1A2-related epileptic encephalopathy as they exclude haploinsufficiency as exclusive genetic mechanism.

* These authors contributed equally to this work.


 
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