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Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome
SLC1A4 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 heterozy...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10270265/ https://www.ncbi.nlm.nih.gov/pubmed/37194416 http://dx.doi.org/10.1002/acn3.51786 |
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author | Pujol‐Giménez, Jonai Mirzaa, Ghayda Blue, Elizabeth E. Albano, Giuseppe Miller, Danny E. Allworth, Aimee Bennett, James T. Byers, Peter H. Chanprasert, Sirisak Chen, Jingheng Doherty, Daniel Folta, Andrew B. Gillentine, Madelyn A. Glass, Ian Hing, Anne Horike‐Pyne, Martha Leppig, Kathleen A. Parhin, Azma Ranchalis, Jane Raskind, Wendy H. Rosenthal, Elisabeth A. Schwarze, Ulrike Sheppeard, Sam Strohbehn, Samuel Sybert, Virginia P. Timms, Andrew Wener, Mark Bamshad, Michael J. Hisama, Fuki M. Jarvik, Gail P. Dipple, Katrina M. Hediger, Matthias A. Stergachis, Andrew B. |
author_facet | Pujol‐Giménez, Jonai Mirzaa, Ghayda Blue, Elizabeth E. Albano, Giuseppe Miller, Danny E. Allworth, Aimee Bennett, James T. Byers, Peter H. Chanprasert, Sirisak Chen, Jingheng Doherty, Daniel Folta, Andrew B. Gillentine, Madelyn A. Glass, Ian Hing, Anne Horike‐Pyne, Martha Leppig, Kathleen A. Parhin, Azma Ranchalis, Jane Raskind, Wendy H. Rosenthal, Elisabeth A. Schwarze, Ulrike Sheppeard, Sam Strohbehn, Samuel Sybert, Virginia P. Timms, Andrew Wener, Mark Bamshad, Michael J. Hisama, Fuki M. Jarvik, Gail P. Dipple, Katrina M. Hediger, Matthias A. Stergachis, Andrew B. |
author_sort | Pujol‐Giménez, Jonai |
collection | PubMed |
description | SLC1A4 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. |
format | Online Article Text |
id | pubmed-10270265 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102702652023-06-16 Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome Pujol‐Giménez, Jonai Mirzaa, Ghayda Blue, Elizabeth E. Albano, Giuseppe Miller, Danny E. Allworth, Aimee Bennett, James T. Byers, Peter H. Chanprasert, Sirisak Chen, Jingheng Doherty, Daniel Folta, Andrew B. Gillentine, Madelyn A. Glass, Ian Hing, Anne Horike‐Pyne, Martha Leppig, Kathleen A. Parhin, Azma Ranchalis, Jane Raskind, Wendy H. Rosenthal, Elisabeth A. Schwarze, Ulrike Sheppeard, Sam Strohbehn, Samuel Sybert, Virginia P. Timms, Andrew Wener, Mark Bamshad, Michael J. Hisama, Fuki M. Jarvik, Gail P. Dipple, Katrina M. Hediger, Matthias A. Stergachis, Andrew B. Ann Clin Transl Neurol Brief Communication SLC1A4 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. John Wiley and Sons Inc. 2023-05-16 /pmc/articles/PMC10270265/ /pubmed/37194416 http://dx.doi.org/10.1002/acn3.51786 Text en © 2023 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Brief Communication Pujol‐Giménez, Jonai Mirzaa, Ghayda Blue, Elizabeth E. Albano, Giuseppe Miller, Danny E. Allworth, Aimee Bennett, James T. Byers, Peter H. Chanprasert, Sirisak Chen, Jingheng Doherty, Daniel Folta, Andrew B. Gillentine, Madelyn A. Glass, Ian Hing, Anne Horike‐Pyne, Martha Leppig, Kathleen A. Parhin, Azma Ranchalis, Jane Raskind, Wendy H. Rosenthal, Elisabeth A. Schwarze, Ulrike Sheppeard, Sam Strohbehn, Samuel Sybert, Virginia P. Timms, Andrew Wener, Mark Bamshad, Michael J. Hisama, Fuki M. Jarvik, Gail P. Dipple, Katrina M. Hediger, Matthias A. Stergachis, Andrew B. Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome |
title | Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome |
title_full | Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome |
title_fullStr | Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome |
title_full_unstemmed | Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome |
title_short | Dominant‐negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome |
title_sort | dominant‐negative variant in slc1a4 causes an autosomal dominant epilepsy syndrome |
topic | Brief Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10270265/ https://www.ncbi.nlm.nih.gov/pubmed/37194416 http://dx.doi.org/10.1002/acn3.51786 |
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