| Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SeSAME syndrome) caused by mutations in KCNJ10. | |
| | |
MedLine Citation:
|
PMID: 19289823 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
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 1q23.2-23.3. 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. These findings define a unique human syndrome, and establish the essential role of basolateral K(+) channels in renal electrolyte homeostasis. |
| | |
Authors:
|
Ute I Scholl; Murim Choi; Tiewen Liu; Vincent T Ramaekers; Martin G Häusler; Joanne Grimmer; Sheldon W Tobe; Anita Farhi; Carol Nelson-Williams; Richard P Lifton |
Related Documents
:
|
19443103 - A case of gerstmann-sträussler-scheinker syndrome with the p105l prion protein gene mu... 19701813 - Virilizing adrenocortical carcinoma in a child with turner syndrome and somatic tp53 ge... 16032773 - Cornelia de lange syndrome in association with a balanced reciprocal translocation invo... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-03-16 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 Apr |
Date Detail:
|
Created Date: 2009-04-08 Completed Date: 2009-05-06 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 5842-7 Citation Subset: IM |
Affiliation:
|
Department of Genetics, The Howard Hughes Medical Institute, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Abnormalities, Multiple
/
etiology,
genetics* Animals Ataxia Chromosomes, Human, Pair 1 Hearing Loss, Sensorineural / genetics Humans Mental Retardation / genetics Mice Mice, Knockout Mutation* Potassium Channels, Inwardly Rectifying / deficiency, genetics*, physiology Seizures / genetics Syndrome Tissue Distribution Water-Electrolyte Balance / genetics |
| Grant Support | |
ID/Acronym/Agency:
|
//Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
|
0/Potassium Channels, Inwardly Rectifying; 0/potassium inwardly-rectifying channel, subfamily J, member 10 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: miR-375 maintains normal pancreatic {alpha}- and {beta}-cell mass.
Next Document: Thinking like a trader selectively reduces individuals' loss aversion.