ArticleHuman molecular genetics2019
De novo loss-of-function KCNMA1 variants are associated with a new multiple malformation syndrome and a broad spectrum of developmental and neurological phenotypes.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Intellectual Disability and Potassium Channelopathies: A Systematic Review.Frontiers in genetics · 2020Pooled it
- Mixed Movement Disorder in a Patient With a Novel Biallelic KCNMA1 Splice-Site Variant: Expanding the Genotype-Phenotype Correlation.Journal of movement disorders · 2026Article
- Case report: Whole-exome sequencing reveals a novel variant in a patient with epilepsy presenting with fever.Frontiers in genetics · 2026Article
- Genetic crosstalk of autism spectrum disorders and epilepsy: an insight into the presynapse.Frontiers in neurology · 2025Article
- Altered trial-to-trial responses to reward outcomes in KCNMA1 knockout mice during probabilistic learning tasks.Behavioral and brain functions : BBF · 2024Article
- Activation of BK channels prevents diabetes-induced osteopenia by regulating mitochondrial CaAutophagy · 2024Article
- Structural mapping of patient-associated KCNMA1 gene variants.Biophysical journal · 2024Article
- Transmembrane determinants of voltage-gating differences between BK (Slo1) and Slo3 channels.Biophysical journal · 2024Article
- Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy.Journal of clinical neurology (Seoul, Korea) · 2024Article
- The BKPhysiological reports · 2024Article
- Epigenetics of the far northern Yakutian population.Clinical epigenetics · 2023Article
- Genomic architecture of autism spectrum disorder in Qatar: The BARAKA-Qatar Study.Genome medicine · 2023Article
- Hyperacusis in the AdultInternational journal of molecular sciences · 2023Article
- Targeting Ion Channels and Purkinje Neuron Intrinsic Membrane Excitability as a Therapeutic Strategy for Cerebellar Ataxia.Life (Basel, Switzerland) · 2023Review
- BK channel modulation by positively charged peptides and auxiliary γ subunits mediated by the Ca2+-bowl site.The Journal of general physiology · 2023Article
- Heteromeric wild-type/mutant potassium channel subunit composition as a major determinant of channelopathy phenotype in heterozygous patients.The Journal of general physiology · 2023Article
- BK channels of five different subunit combinations underlie the de novo KCNMA1 G375R channelopathy.The Journal of general physiology · 2023Article
- AGGF1 therapy inhibits thoracic aortic aneurysms by enhancing integrin α7-mediated inhibition of TGF-β1 maturation and ERK1/2 signaling.Nature communications · 2023Article
- An epigenetic synopsis of parental substance use.Epigenomics · 2023Review
- KCurrent neuropharmacology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 14 institutions in 4 countries.
Funding
Abstract
KCNMA1 encodes the large-conductance Ca2+- and voltage-activated K+ (BK) potassium channel α-subunit, and pathogenic gain-of-function variants in this gene have been associated with a dominant form of generalized epilepsy and paroxysmal dyskinesia. Here, we genetically and functionally characterize eight novel loss-of-function (LoF) variants of KCNMA1. Genome or exome sequencing and the participation in the international Matchmaker Exchange effort allowed for the identification of novel KCNMA1 variants. Patch clamping was used to assess functionality of mutant BK channels. The KCNMA1 variants p.(Ser351Tyr), p.(Gly356Arg), p.(Gly375Arg), p.(Asn449fs) and p.(Ile663Val) abolished the BK current, whereas p.(Cys413Tyr) and p.(Pro805Leu) reduced the BK current amplitude and shifted the activation curves toward positive potentials. The p.(Asp984Asn) variant reduced the current amplitude without affecting kinetics. A phenotypic analysis of the patients carrying the recurrent p.(Gly375Arg) de novo missense LoF variant revealed a novel syndromic neurodevelopmental disorder associated with severe developmental delay, visceral and cardiac malformations, connective tissue presentations with arterial involvement, bone dysplasia and characteristic dysmorphic features. Patients with other LoF variants presented with neurological and developmental symptoms including developmental delay, intellectual disability, ataxia, axial hypotonia, cerebral atrophy and speech delay/apraxia/dysarthria. Therefore, LoF KCNMA1 variants are associated with a new syndrome characterized by a broad spectrum of neurological phenotypes and developmental disorders. LoF variants of KCNMA1 cause a new syndrome distinctly different from gain-of-function variants in the same gene.
Indexed as
Identifiers
What OpenQuestion holds
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.