ArticleAmerican journal of human genetics1995
Spectrum of mutations in the major human skeletal muscle chloride channel gene (CLCN1) leading to myotonia.
Article in American journal of human genetics, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 165 citations in OpenAlex.
- Novel deep intronic variant in CLCN1 causing autosomal recessive myotonia congenita.Neurogenetics · 2026Article
- Whole Exome Sequencing Reveals Candidate Variants in Ion Channel Genes for Pelvic Muscle Dysfunction in Young Females with a Family History.International urogynecology journal · 2025Article
- Structural basis of pH-dependent activation in a CLC transporter.Nature structural & molecular biology · 2024Article
- Case report: Multiple approach analysis in a case of clinically assessed myotonia congenita.Frontiers in genetics · 2024Article
- ClC-1 Chloride Channel: Inputs on the Structure-Function Relationship of Myotonia Congenita-Causing Mutations.Biomedicines · 2023Review
- Clinical analysis in patients withFrontiers in neurology · 2023Article
- Clinical and molecular characteristics of myotonia congenita in China: Case series and a literature review.Channels (Austin, Tex.) · 2022Review
- A novel mutation of the CLCN1 gene in a cat with myotonia congenita: Diagnosis and treatment.Journal of veterinary internal medicine · 2022Article
- Case report: Sodium and chloride muscle channelopathy coexistence: A complicated phenotype and a challenging diagnosis.Frontiers in neurology · 2022Article
- Association of Three Different Mutations in the CLCN1 Gene Modulating the Phenotype in a Consanguineous Family with Myotonia Congenita.Journal of molecular neuroscience : MN · 2021Article
- Saturation mutagenesis defines novel mouse models of severe spine deformity.Disease models & mechanisms · 2021Article
- Genetic cause of heterogeneous inherited myopathies in a cohort of Greek patients.Molecular genetics and metabolism reports · 2020Article
- Pathomechanisms of aFrontiers in neurology · 2020Article
- Defective Gating and Proteostasis of Human ClC-1 Chloride Channel: Molecular Pathophysiology of Myotonia Congenita.Frontiers in neurology · 2020Review
- Myotonia congenita: mutation spectrum ofJournal of genetics · 2019Article
- An Up-to-Date Overview of the Complexity of Genotype-Phenotype Relationships in Myotonic Channelopathies.Frontiers in neurology · 2019Review
- Skeletal Muscle Channelopathies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
- A case report: autosomal recessive Myotonia congenita caused by a novel splice mutation (c.1401 + 1G > A) in CLCN1 gene of a Chinese Han patient.BMC neurology · 2018Article
- Coexistence of CLCN1 and SCN4A mutations in one family suffering from myotonia.Neurogenetics · 2017Article
- Sequence CLCN1 and SCN4A in patients with Nondystrophic myotonias in Chinese populations: Genetic and pedigree analysis of 10 families and review of the literature.Channels (Austin, Tex.) · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Autosomal dominant myotonia congenita and autosomal recessive generalized myotonia (GM) are genetic disorders characterized by the symptom of myotonia, which is based on an electrical instability of the muscle fiber membrane. Recently, these two phenotypes have been associated with mutations in the major muscle chloride channel gene CLCN1 on human chromosome 7q35. We have systematically screened the open reading frame of the CLCN1 gene for mutations by SSC analysis (SSCA) in a panel of 24 families and 17 single unrelated patients with human myotonia. By direct sequencing of aberrant SSCA conformers were revealed 15 different mutations in a total of 18 unrelated families and 13 single patients. Of these, 10 were novel (7 missense mutations, 2 mutations leading to frameshift, and 1 mutation predicted to affect normal splicing). In our overall sample of 94 GM chromosomes we were able to detect 48 (51%) mutant GM alleles. Three mutations (F413C), R894X, and a 14-bp deletion in exon 13) account for 32% of the GM chromosomes in the German population. Our finding that A437T is probably a polymorphism is in contrast to a recent report that the recessive phenotype GM is associated with this amino acid change. We also demonstrate that the R894X mutation may act as a recessive or a dominant mutation in the CLCN1 gene, probably depending on the genetic background. Functional expression of the R894X mutant in Xenopus oocytes revealed a large reduction, but not complete abolition, of chloride currents. Further, it had a weak dominant negative effect on wild-type currents in coexpression studies. Reduction of currents predicted for heterozygous carriers are close to the borderline value, which is sufficient to elicit myotonia.
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8533761PMC1801423W1573790830What 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.