Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum.

Nature genetics | Nov 31, 2002

http://www.ncbi.nlm.nih.gov/pubmed/12368912

Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) is a severe sensorimotor neuropathy associated with mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. ACCPN is transmitted in an autosomal recessive fashion and is found at a high frequency in the province of Quebec, Canada. ACCPN has been previously mapped to chromosome 15q. The gene SLC12A6 (solute carrier family 12, member 6), which encodes the K+-Cl- transporter KCC3 and maps within the ACCPN candidate region, was screened for mutations in individuals with ACCPN. Four distinct protein-truncating mutations were found: two in the French Canadian population and two in non-French Canadian families. The functional consequence of the predominant French Canadian mutation (2436delG, Thr813fsX813) was examined by heterologous expression of wildtype and mutant KCC3 in Xenopus laevis oocytes; the truncated mutant is appropriately glycosylated and expressed at the cellular membrane, where it is non-functional. Mice generated with a targeted deletion of Slc12a6 have a locomotor deficit, peripheral neuropathy and a sensorimotor gating deficit, similar to the human disease. Our findings identify mutations in SLC12A6 as the genetic lesion underlying ACCPN and suggest a critical role for SLC12A6 in the development and maintenance of the nervous system.

Pubmed ID: 12368912 RIS Download

Mesh terms: Agenesis of Corpus Callosum | Animals | Blotting, Southern | Brain | Canada | Chromosomes, Human, Pair 15 | Corpus Callosum | Exons | Gene Deletion | Genes, Recessive | Haplotypes | Homozygote | Humans | Immunoblotting | Mice | Mice, Knockout | Microscopy, Fluorescence | Models, Genetic | Molecular Sequence Data | Mutation | Open Reading Frames | Peripheral Nervous System Diseases | Phenotype | Polymorphism, Genetic | Recombination, Genetic | Reverse Transcriptase Polymerase Chain Reaction | Sequence Analysis, DNA | Sodium-Potassium-Chloride Symporters | Spinal Cord | Symporters | Time Factors | Xenopus

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

None

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.