Alkalosis

Researchers from Yale University report details of new studies and findings in the area of mental retardation

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"Direct DNA sequencing of KCNJ10, which encodes an inwardly rectifying K+ channel, identifies previously unidentified missense or nonsense mutations on both alleles in all affected subjects. These mutations alter highly conserved amino acids and are absent among control chromosomes. Many of these mutations have been shown to cause loss of function in related K+ channels. These findings demonstrate that loss-of-function mutations in KCNJ10 cause this syndrome, which we name SeSAME. KCNJ10 is expressed in glia in the brain and spinal cord, where it is believed to take up K+ released by neuronal repolarization, in cochlea, where it is involved in the generation of endolymph, and on the basolateral membrane in the distal nephron. We propose that KCNJ10 is required in the kidney for normal salt reabsorption in the distal convoluted tubule because of the need for K+ recycling across the basolateral membrane to enable normal activity of the Na+-K+-ATPase; loss of this function accounts for the observed electrolyte defects. Mice deficient for KCNJ10 show a related phenotype with seizures, ataxia, and hearing loss, further supporting KCNJ10's role in this syndrome," wrote U.I. Scholl and colleagues, Yale University.

The researchers concluded: "These findings define a unique human syndrome, and establish the essential role of basolateral K+ channels in renal electrolyte homeostasis."

Scholl and colleagues published their study in Proceedings of the National Academy of Sciences of the United States of America (Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. Proceedings of the National Academy of Sciences of the United States of America, 2009;106(14):5842-5847).

For more information, contact R.P. Lifton, Yale University, School Medical, Howard Hughes Med Institute, Dept. of Genetics, 333 Cedar St., New Haven, CT 06510, USA.

Publisher contact information for the journal Proceedings of the National Academy of Sciences of the United States of America is: National Acad Sciences, 2101 Constitution Avenue NW, Washington, DC 20418, USA.

Keywords: United States, New Haven, Alkalosis, Amino Acids, Ataxia, DNA Research, DNA Sequence Proteomics, Deafness, Deoxyribonucleic Acid, Developmental Disabilities, Drugs, Gitelman's Syndrome, Hypokalemia, Kidney, Mental Retardation, Nephrology, Pharmaceuticals, Seizures, Therapy, Treatment, Yale University.

This article was prepared by Biotech Business Week editors from staff and other reports. Copyright 2009, Biotech Business Week via NewsRx.com.