Evidence map›Paper›PMID 37194416›Full record

ArticleAnnals of clinical and translational neurology2023

Dominant-negative variant in SLC1A4 causes an autosomal dominant epilepsy syndrome.

Jonai Pujol-Giménez, Ghayda Mirzaa, Elizabeth E Blue, Giuseppe Albano, Danny E Miller, Aimee Allworth, James T Bennett, Peter H Byers, Sirisak Chanprasert, Jingheng Chen and 24 more

Registry-linked trialOpen access · goldAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of clinical and translational neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02450851 (Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02450851 recruitingnot on this map

Clinical and Genetic Evaluation of Patients With Undiagnosed Disorders Through the Undiagnosed Diseases Network

TypeobservationalSponsorNational Human Genome Research Institute (NHGRI)Ran2015 to 2028Enrolled20,000ConditionsGenetic Disease
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Case Report of Dual Variants inClinical case reports · 2026
    Article
  3. Review
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

34 authors at 4 institutions in 2 countries.

Jonai Pujol-GiménezDepartment of Nephrology and Hypertension, University Hospital Bern, Inselspital, Bern, Switzerland.
Ghayda MirzaaCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Elizabeth E BlueBrotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
Giuseppe AlbanoDepartment of Nephrology and Hypertension, University Hospital Bern, Inselspital, Bern, Switzerland.
Danny E MillerDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Aimee AllworthUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
James T BennettCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Peter H ByersUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Sirisak ChanprasertUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Jingheng ChenDepartment of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.
Daniel DohertyDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Andrew B FoltaUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Madelyn A GillentineDepartment of Laboratories, Seattle Children's Hospital, Seattle, Washington, USA.
Ian GlassDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Anne HingDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Martha Horike-PyneUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Kathleen A LeppigGroup Health Cooperative, Kaiser Permanente Washington, Seattle, Washington, USA.
Azma ParhinUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Jane RanchalisUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Wendy H RaskindUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Elisabeth A RosenthalUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Ulrike SchwarzeDepartment of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
Sam SheppeardUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Samuel StrohbehnUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Virginia P SybertUniversity of Washington, Institute of Public Health Genetics, Seattle, Washington, USA.
Andrew TimmsCenter for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, Washington, USA.
Mark WenerDepartment of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.
University of Washington Center for Mendelian Genomics (UW-CMG)a, Undiagnosed Diseases Network (UDN)
Michael J BamshadDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Fuki M HisamaBrotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
Gail P JarvikBrotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
Katrina M DippleDepartment of Pediatrics, University of Washington, Seattle, Washington, USA.
Matthias A HedigerDepartment of Nephrology and Hypertension, University Hospital Bern, Inselspital, Bern, Switzerland.
Andrew B StergachisBrotman Baty Institute for Precision Medicine, Seattle, Washington, USA.ORCID 0000-0002-1299-3674
University of Washington · USSeattle Children's Hospital · USUniversity of Bern · CHGroup Health Cooperative · US

Funding

UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
UCLA clinical site for the investigation of undiagnosed disordersU01HG007703 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2014 to 2022
$10.1M
Pacific Northwest Undiagnosed Diseases Network Clinical SiteU01HG010233 · NHGRI · UNIVERSITY OF WASHINGTON · PI DIPPLE, KATRINA M, JARVIK, GAIL PAIRITZ · 2018 to 2022
$5.4M
Pacific Northwest Undiagnosed Diseases Network Clinical SiteU01NS134355 · NINDS · UNIVERSITY OF WASHINGTON · PI ELIZABETH ELOYCE BLUE, Katrina M Dipple · 2023 to 2026
$3.0M
Investigating the contribution of non-coding genetic variation to rare disordersDP5OD029630 · OD · UNIVERSITY OF WASHINGTON · PI STERGACHIS, ANDREW BEN · 2020 to 2024
$1.9M
UCLA clinical site for the investigation of undiagnosed disordersU01NS134356 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MARTINEZ-AGOSTO, JULIAN, NELSON, STANLEY F. · 2023 to 2023
$936k
NHGRI NIH HHS U01 HG007703NHGRI NIH HHS U01 HG010233NHGRI NIH HHS UM1 HG006493NIH HHS DP5 OD029630NINDS NIH HHS U01 NS134355NINDS NIH HHS U01 NS134356
6 · The paper itself

Abstract

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.

Indexed as

EpilepsyEpileptic SyndromesMicrocephalyAmino Acid Transport System ASCChildHeterozygoteHumansSerineAmino Acid Transport System ASCSerineSLC1A4 protein, human

Identifiers

PMID37194416
PMCPMC10270265
OpenAlexW4376873055

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.