Project description:Voltage-gated ClC chloride channels play important roles in cell volume regulation, control of muscle excitability, and probably transepithelial transport. ClC channels can be functionally expressed without other subunits, but it is unknown whether they function as monomers. We now exploit the properties of human mutations in the muscle chloride channel, ClC-1, to explore its multimeric structure. This is based on analysis of the dominant negative effects of ClC-1 mutations causing myotonia congenita (MC, Thomsen's disease), including a newly identified mutation (P480L) in Thomsen's own family. In a co-expression assay, Thomsen's mutation dramatically inhibits normal ClC-1 function. A mutation found in Canadian MC families (G230E) has a less pronounced dominant negative effect, which can be explained by functional WT/G230E heterooligomeric channels with altered kinetics and selectivity. Analysis of both mutants shows independently that ClC-1 functions as a homooligomer with most likely four subunits.

| S-EPMC394869 | biostudies-other

Clinical Utility Gene Card for: autosomal recessive cone-rod dystrophy.

Project description: Not available

| S-EPMC4795210 | biostudies-literature

Clinical utility gene card for McArdle disease.

Project description:Name of the disease (synonyms) McArdle disease (glycogenosis type V; glycogen storage disease V (GSDV); PYGM deficiency; muscle glycogen phosphorylase deficiency; myophosphorylase deficiency). OMIM# of the disease #232600. Name of the analysed genes or DNA/chromosome segments Muscle glycogen phosphoryalse (PYGM). OMIM# of the gene(s) #608455.Review of the analytical and clinical validity as well as of the clinical utility of DNA-based testing for variants in the PYGM gene(s) in⊠ diagnostic,⊠ predictive and⊠ prenatal settings and for⊠ risk assessment in relatives.

| S-EPMC5945672 | biostudies-literature

Clinical utility gene card for: Huntington's disease.

Project description: Not available

| S-EPMC3992568 | biostudies-literature

Clinical utility gene card for: Fabry disease - update 2016.

Project description: Not available

| S-EPMC5520062 | biostudies-literature

Myotonia congenita: novel mutations in CLCN1 gene.

Project description:Myotonia congenita belongs to the group of non-dystrophic myotonia caused by mutations of CLCN1gene, which encodes human skeletal muscle chloride channel 1. It can be inherited either in autosomal dominant (Thomsen disease) or recessive (Becker disease) forms. Here we have sequenced all 23 exons and exon-intron boundaries of the CLCN1 gene, in a panel of 5 unrelated Chinese patients with myotonia congenita (2 with dominant and 3 with recessive form). In addition, detailed clinical analysis was performed in these patients to summarize their clinical characteristics in relation to their genotypes. Mutational analyses revealed 7 different point mutations. Of these, we have found 3 novel mutations including 2 missense (R47W, V229M), one splicing (IVS19+2T>C), and 4 known mutations (Y261C,G523D, M560T, G859D). Our data expand the spectrum of CLCN1 mutations and provide insights for genotype-phenotype correlations of myotonia congenita in the Chinese population.

| S-EPMC4826137 | biostudies-literature

Clinical utility gene card for: cystinosis.

Project description: Not available

| S-EPMC3992566 | biostudies-literature

Clinical utility gene card for: choroideremia.

Project description: Not available

| S-EPMC3953909 | biostudies-literature