CLCN7

CLCN7

A gene on chromosome 16p13 that encodes a member of the voltage-gated chloride channel and ion transporters.

Molecular pathology
CLCN7 mutations cause autosomal dominant osteopetrosis type 2 (OPTA2), also known as autosomal dominant Albers-Schonberg disease—which is the most common form of osteopetrosis—as well as causing autosomal recessive type 4 (OPTB4); both are characterised by defective resorption of immature bone.
References in periodicals archive ?
ARO can result from mutations in the TCIRG1 gene (T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein a isoform 3) (3) the CLCN7 gene (chloride channel 7) (4) the OSTM1 gene (osteopetrosis-associated transmembrane protein 1) (5) the TNFSF11 gene (tumour necrosis factor ligand superfamily, member 11 encoding receptor activator for nuclear factor kappa b ligand, RANKL) (6), the TNFRSF11A gene (tumour necrosis factor ligand superfamily, member 11A encoding receptor activator of nuclear factor-kappa B, RANK) (7) or PLEKHM1 gene (pleckstrin homology domain-containing protein, family M, member) (8) and CA2 gene (carbonic anhydrase II) (9).
Most ARO cases have been ascribed to mutations in the TCIRG1 gene and only a few cases have been ascribed to mutations in the CLCN7 gene (10).
In our previous study, we were able to prioritize the CLCN7 loci for mutational analysis based on the history of consanguinity, by performing a whole genome scan for homozygous chromosomal regions,using single-nucleotidepolymorphism(SNP) microarrays (13,14).
Other genes mutated in ARO are CLCN7 and OSTM1, that together form a chloride channel or chloride/proton-exchanger which also resides in the ruffled membrane and facilitates acidification (5,6).
Mutation analysis: Patient DNAs were investigated for mutations in the genes TCIRGl (ATP6V0A3) and CLCN7 by amplifying all exons and flanking intronic regions by PCR using genomic DNA as a template.
Mutations on both alleles of the genes TCIRGl or CLCN7 were detected in all eight cases.
Since CLCN7 mutations were identified in this case, it is also possible that the seizures were a sign of neuronopathic changes, which are more frequent if CLCN7 mutations are present (17).