{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:18:21Z","timestamp":1792523901617,"version":"4.5.0"},"reference-count":36,"publisher":"National Academy of Sciences","issue":"14","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,4,7]]},"abstract":"<jats:p>\n                    We describe members of 4 kindreds with a previously unrecognized syndrome characterized by seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (hypokalemia, metabolic alkalosis, and hypomagnesemia). By analysis of linkage we localize the putative causative gene to a 2.5-Mb segment of chromosome 1q23.2\u201323.3. Direct DNA sequencing of\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    , which encodes an inwardly rectifying K\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:sup>+<\/jats:sup>\n                    channels. These findings demonstrate that loss-of-function mutations in\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    cause this syndrome, which we name SeSAME.\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    is expressed in glia in the brain and spinal cord, where it is believed to take up K\n                    <jats:sup>+<\/jats:sup>\n                    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\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    is required in the kidney for normal salt reabsorption in the distal convoluted tubule because of the need for K\n                    <jats:sup>+<\/jats:sup>\n                    recycling across the basolateral membrane to enable normal activity of the Na\n                    <jats:sup>+<\/jats:sup>\n                    -K\n                    <jats:sup>+<\/jats:sup>\n                    -ATPase; loss of this function accounts for the observed electrolyte defects. Mice deficient for\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    show a related phenotype with seizures, ataxia, and hearing loss, further supporting\n                    <jats:italic>KCNJ10<\/jats:italic>\n                    's role in this syndrome. These findings define a unique human syndrome, and establish the essential role of basolateral K\n                    <jats:sup>+<\/jats:sup>\n                    channels in renal electrolyte homeostasis.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0901749106","type":"journal-article","created":{"date-parts":[[2009,3,16]],"date-time":"2009-03-16T21:38:29Z","timestamp":1237239509000},"page":"5842-5847","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":471,"title":["Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in\n                    <i>KCNJ10<\/i>"],"prefix":"10.1073","volume":"106","author":[{"given":"Ute I.","family":"Scholl","sequence":"first","affiliation":[{"name":"Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murim","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiewen","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent T.","family":"Ramaekers","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Centre Hospitalier Universitaire, Domaine Universitaire du Sart Tilman, B\u00e2timent B 35, B-4000 Li\u00e8ge 1, Belgium;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin G.","family":"H\u00e4usler","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University Hospital, RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Grimmer","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X8; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheldon W.","family":"Tobe","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON, Canada M4N 3M5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Farhi","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Nelson-Williams","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard P.","family":"Lifton","sequence":"additional","affiliation":[{"name":"Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 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