ArticleBrain : a journal of neurology2020
SLC12A2 variants cause a neurodevelopmental disorder or cochleovestibular defect.
Article in Brain : a journal of neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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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.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Mutation Spectrum and Novel Rare Variants in a Han Chinese Hearing Loss Cohort Using a Tiered Sequencing Strategy.Molecular genetics & genomic medicine · 2026Article
- Chasing the ghost in the code: highlighting the mystery of a rare genetic condition.American journal of physiology. Cell physiology · 2026Review
- Complete omission of exon 21 from Slc12a2 transcripts in mice results in hearing loss.Scientific reports · 2025Article
- Heterozygous Missense Variants in the ATPase Phospholipid Transporting 9A Gene,Human mutation · 2025Article
- A data-mining analysis of host solute carrier family proteins in SARS-CoV-2 infection with reference to brain endothelial cells and the blood-brain barrier in COVID-19.Frontiers in neurology · 2025Article
- Development of patient-specific iPSC-based epilepsy models and identification of differentially expressed genes for disease mechanisms.Frontiers in neuroscience · 2025Article
- Cation Chloride Cotransporter NKCC1 Operates through a Rocking-Bundle Mechanism.Journal of the American Chemical Society · 2024Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Frequency and Phenotype ofNeurology · 2023Article
- 3' UTR Deletion ofGenes · 2023Article
- NKCC1 in human diseases: is theAmerican journal of physiology. Cell physiology · 2023Article
- Age-appropriate potassium clearance from perinatal cerebrospinal fluid depends on choroid plexus NKCC1.Fluids and barriers of the CNS · 2023Article
- New year, new genes.European journal of human genetics : EJHG · 2023Article
- Inhibition mechanism of NKCC1 involves the carboxyl terminus and long-range conformational coupling.Science advances · 2022Article
- A Survey of the Metabolic Landscape of the Developing Cerebellum at Single-Cell Resolution.Cerebellum (London, England) · 2022Article
- Loss of NKCC1 function increases epithelial tight junction permeability by upregulating claudin-2 expression.American journal of physiology. Cell physiology · 2022Article
- Article
- NKCC1 Deficiency in Forming Hippocampal Circuits Triggers Neurodevelopmental Disorder: Role of BDNF-TrkB Signalling.Brain sciences · 2022Review
- NKCC1 and KCC2: Structural insights into phospho-regulation.Frontiers in molecular neuroscience · 2022Review
- How Staying Negative Is Good for the (Adult) Brain: Maintaining Chloride Homeostasis and the GABA-Shift in Neurological Disorders.Frontiers in molecular neuroscience · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 12 institutions in 4 countries.
Funding
Abstract
The SLC12 gene family consists of SLC12A1-SLC12A9, encoding electroneutral cation-coupled chloride co-transporters. SCL12A2 has been shown to play a role in corticogenesis and therefore represents a strong candidate neurodevelopmental disorder gene. Through trio exome sequencing we identified de novo mutations in SLC12A2 in six children with neurodevelopmental disorders. All had developmental delay or intellectual disability ranging from mild to severe. Two had sensorineural deafness. We also identified SLC12A2 variants in three individuals with non-syndromic bilateral sensorineural hearing loss and vestibular areflexia. The SLC12A2 de novo mutation rate was demonstrated to be significantly elevated in the deciphering developmental disorders cohort. All tested variants were shown to reduce co-transporter function in Xenopus laevis oocytes. Analysis of SLC12A2 expression in foetal brain at 16-18 weeks post-conception revealed high expression in radial glial cells, compatible with a role in neurogenesis. Gene co-expression analysis in cells robustly expressing SLC12A2 at 16-18 weeks post-conception identified a transcriptomic programme associated with active neurogenesis. We identify SLC12A2 de novo mutations as the cause of a novel neurodevelopmental disorder and bilateral non-syndromic sensorineural hearing loss and provide further data supporting a role for this gene in human neurodevelopment.
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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.