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

Matias Wagner; Mirjana Gusic; Roman Günthner; Bader Alhaddad; Reka Kovacs-Nagy; Christine Makowski; Friedrich Baumeister; Tim Strom; Thomas Meitinger; Holger Prokisch; Saskia B. Wortmann

doi:10.1055/s-0037-1606370

Neuropediatrics, Inhaltsverzeichnis

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^*

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

²Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

³Institut für Neurogenomik, Helmholtz Zentrum München, Neuherberg, Germany

,

Mirjana Gusic^*

²Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

,

Roman Günthner

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

⁴Department of Nephrology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

,

Bader Alhaddad

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

,

Reka Kovacs-Nagy

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

,

Christine Makowski

⁵Department of Pediatrics, Technische Universität München, Munich, Germany

,

Friedrich Baumeister

⁶Children's Hospital, RoMed Klinikum, Rosenheim, Germany

,

Tim Strom

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

²Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

,

Thomas Meitinger

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

²Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

,

Holger Prokisch^*

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

²Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

,

Saskia B. Wortmann^*

¹Institute of Human Genetics, Technische Universität München, Munich, Germany

²Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany

⁷Department of Pediatrics, Salzburger Landeskliniken (SALK) and Paracelsus Medical University, Salzburg, Austria

› Institutsangaben

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.

Keywords

epilepsy - seizure - visual impairment - SLC1A2 - exome sequencing

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