Dominant‐negative variant in <i>SLC1A4</i> causes an autosomal dominant epilepsy syndrome-Reference-Cited by-同舟云学术

Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome

Published:2023-05-16 Issue:6 Volume:10 Page:1046-1053
ISSN:2328-9503
Container-title:Annals of Clinical and Translational Neurology
language:en
Short-container-title:Ann Clin Transl Neurol

Author:

Pujol‐Giménez Jonai¹²,Mirzaa Ghayda³⁴⁵,Blue Elizabeth E.⁵⁶⁷,Albano Giuseppe¹²,Miller Danny E.⁴⁵⁸,Allworth Aimee⁶,Bennett James T.³⁴⁵⁹,Byers Peter H.⁶⁸,Chanprasert Sirisak⁶,Chen Jingheng⁷,Doherty Daniel⁴⁵,Folta Andrew B.⁶,Gillentine Madelyn A.¹⁰,Glass Ian⁴⁵,Hing Anne⁴,Horike‐Pyne Martha⁶,Leppig Kathleen A.¹¹,Parhin Azma⁶,Ranchalis Jane⁶,Raskind Wendy H.⁶,Rosenthal Elisabeth A.⁶,Schwarze Ulrike⁸,Sheppeard Sam⁶,Strohbehn Samuel⁶,Sybert Virginia P.⁶,Timms Andrew⁹,Wener Mark⁸,Bamshad Michael J.⁴⁵,Hisama Fuki M.⁵⁶,Jarvik Gail P.⁵⁶¹²,Dipple Katrina M.⁴⁵,Hediger Matthias A.¹²,Stergachis Andrew B.⁵⁶¹²^ORCID,

Affiliation:

1. Department of Nephrology and Hypertension University Hospital Bern, Inselspital Bern Switzerland

2. Department of Biomedical Research University of Bern Bern Switzerland

3. Center for Integrative Brain Research Seattle Children's Research Institute Seattle Washington USA

4. Department of Pediatrics University of Washington Seattle Washington USA

5. Brotman Baty Institute for Precision Medicine Seattle Washington USA

6. University of Washington, Institute of Public Health Genetics Seattle Washington USA

7. Department of Laboratory Medicine and Pathology University of Washington School of Medicine Seattle Washington USA

8. Department of Medicine University of Washington School of Medicine Seattle Washington USA

9. Center for Developmental Biology and Regenerative Medicine Seattle Children's Research Institute Seattle Washington USA

10. Department of Laboratories Seattle Children's Hospital Seattle Washington USA

11. Group Health Cooperative Kaiser Permanente Washington Seattle Washington USA

12. Genome Sciences University of Washington School of Medicine Seattle Washington USA

Abstract

AbstractSLC1A4 is a trimeric neutral amino acid transporter essential for shuttling L‐serine from astrocytes into neurons. Individuals with biallelic variants in SLC1A4 are known to have spastic tetraplegia, thin corpus callosum, and progressive microcephaly (SPATCCM) syndrome, but individuals with heterozygous variants are not thought to have disease. We identify an 8‐year‐old patient with global developmental delay, spasticity, epilepsy, and microcephaly who has a de novo heterozygous three amino acid duplication in SLC1A4 (L86_M88dup). We demonstrate that L86_M88dup causes a dominant‐negative N‐glycosylation defect of SLC1A4, which in turn reduces the plasma membrane localization of SLC1A4 and the transport rate of SLC1A4 for L‐serine.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

National Institutes of Health

Burroughs Wellcome Fund

National Human Genome Research Institute

Publisher

Wiley

Subject

Neurology (clinical),General Neuroscience

Link

https://onlinelibrary.wiley.com/doi/pdf/10.1002/acn3.51786

Reference16 articles.

1. A rare cause of microcephaly, thin corpus callosum and refractory epilepsy due to a novel SLC1A4 gene mutation

2. A Novel SLC1A4 Mutation (p.Y191*) Causes Spastic Tetraplegia, Thin Corpus Callosum, and Progressive Microcephaly (SPATCCM) With Seizure Disorder

3. Severe neurodevelopmental disorder with intractable seizures due to a novel SLC1A4 homozygous variant

4. A novel SLC1A4 homozygous mutation causing congenital microcephaly, epileptic encephalopathy and spastic tetraparesis: a video-EEG and tractography – case study

5. A homozygous mutation inSLC1A4in siblings with severe intellectual disability and microcephaly