ArticleJournal of human genetics2016
De novo missense mutations in NALCN cause developmental and intellectual impairment with hypotonia.
Article in Journal of human genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- Transcriptomic profiling of DYT-TOR1A patient-derived iPSC reveals dysregulation in extracellular matrix, lipid metabolism, and Chr22q11.23.BMC medical genomics · 2025Article
- New presentation of CLIFAHDD syndrome with a novel variant inClinical case reports · 2023Article
- NALCN is a potential biomarker and therapeutic target in human cancers.Frontiers in genetics · 2023Article
- Architecture of the human NALCN channelosome.Cell discovery · 2022Article
- Central Apneas Due to the CLIFAHDD Syndrome Successfully Treated with Pyridostigmine.International journal of environmental research and public health · 2022Article
- Case Report: AFrontiers in pediatrics · 2022Article
- Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.PLoS genetics · 2021Article
- Elevated Expression and Activity of Sodium Leak Channel Contributes to Neuronal Sensitization of Inflammatory Pain in Rats.Frontiers in molecular neuroscience · 2021Article
- Structure of voltage-modulated sodium-selective NALCN-FAM155A channel complex.Nature communications · 2020Article
- Structure of the human sodium leak channel NALCN in complex with FAM155A.Nature communications · 2020Article
- The NALCN Channel Regulator UNC-80 Functions in a Subset of Interneurons To RegulateG3 (Bethesda, Md.) · 2020Article
- Methylation determines the extracellular calcium sensitivity of the leak channel NALCN in hippocampal dentate granule cells.Experimental & molecular medicine · 2019Article
- Long-read assembly of the Chinese rhesus macaque genome and identification of ape-specific structural variants.Nature communications · 2019Article
- Functional expression of CLIFAHDD and IHPRF pathogenic variants of the NALCN channel in neuronal cells reveals both gain- and loss-of-function properties.Scientific reports · 2019Article
- Dopamine negatively modulates the NCA ion channels in C. elegans.PLoS genetics · 2017Article
- The NCA-1 and NCA-2 Ion Channels Function Downstream of GGenetics · 2017Article
- NovelAnnals of clinical and translational neurology · 2016Article
- NALCN channelopathies: Distinguishing gain-of-function and loss-of-function mutations.Neurology · 2016Article
- Article
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Three recessive mutations in the sodium leak channel, nonselective (NALCN) have been reported to cause intellectual disability and hypotonia. In addition, 14 de novo heterozygous mutations have been identified in 15 patients with arthrogryposis and neurodevelopmental impairment. Here, we report three patients with neurodevelopmental disease and hypotonia, harboring one recurrent (p.R1181Q) and two novel mutations (p.L312V and p.V1020F) occurring de novo in NALCN. Mutation p.L312 is located in the pore forming S6 region of domain I and p.V1020F in the S5 region of domain III. Mutation p.R1181Q is in a linker region. Mapping these three mutations to a model of NALCN showed p.Leu312 and p.Val1020 positioned in the hydrophobic core of the pore modules, indicating these two mutations may affect the gating function of NALCN. Although p.R1181Q is unlikely to affect the ion channel structure, previous studies have shown that an analogous mutation in Caenorhabditis elegans produced a phenotype with a coiling locomotion, suggesting that p.R1181Q could also affect NALCN function. Our three patients showed profound intellectual disability and growth delay, facial dysmorphologies and hypotonia. The present data support previous work suggesting heterozygous NALCN mutations lead to syndromic neurodevelopmental impairment.
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