Matches in SemOpenAlex for { <https://semopenalex.org/work/W2004413954> ?p ?o ?g. }
- W2004413954 endingPage "247" @default.
- W2004413954 startingPage "239" @default.
- W2004413954 abstract "The inwardly-rectifying potassium channel Kir4.1 is a major player in the astrocyte-mediated regulation of [K(+)](o) in the brain, which is essential for normal neuronal activity and synaptic functioning. KCNJ10, encoding Kir4.1, has been recently linked to seizure susceptibility in humans and mice, and is a possible candidate gene for Autism Spectrum Disorders (ASD). In this study, we performed a mutational screening of KCNJ10 in 52 patients with epilepsy of unknown cause associated with impairment of either cognitive or communicative abilities, or both. Among them, 14 patients fitted the diagnostic criteria for ASD. We identified two heterozygous KCNJ10 mutations (p.R18Q and p.V84M) in three children (two unrelated families) with seizures, ASD, and intellectual disability. The mutations replaced amino acid residues that are highly conserved throughout evolution and were undetected in about 500 healthy chromosomes. The effects of mutations on channel activity were functionally assayed using a heterologous expression system. These studies indicated that the molecular mechanism contributing to the disorder relates to an increase in either surface-expression or conductance of the Kir4.1 channel. Unlike previous syndromic associations of genetic variants in KCNJ10, the pure neuropsychiatric phenotype in our patients suggests that the new mutations affect K(+) homeostasis mainly in the brain, by acting through gain-of-function defects. Dysfunction in astrocytic-dependent K(+) buffering may contribute to autism/epilepsy phenotype, by altering neuronal excitability and synaptic function, and may represent a new target for novel therapeutic approaches." @default.
- W2004413954 created "2016-06-24" @default.
- W2004413954 creator A5009749641 @default.
- W2004413954 creator A5009870571 @default.
- W2004413954 creator A5023190360 @default.
- W2004413954 creator A5031328703 @default.
- W2004413954 creator A5032251695 @default.
- W2004413954 creator A5039589628 @default.
- W2004413954 creator A5051190122 @default.
- W2004413954 creator A5063072126 @default.
- W2004413954 creator A5068237948 @default.
- W2004413954 creator A5074574580 @default.
- W2004413954 creator A5077772772 @default.
- W2004413954 date "2011-07-01" @default.
- W2004413954 modified "2023-09-24" @default.
- W2004413954 title "Autism with Seizures and Intellectual Disability: Possible Causative Role of Gain-of-function of the Inwardly-Rectifying K+ Channel Kir4.1" @default.
- W2004413954 cites W1548862642 @default.
- W2004413954 cites W1586815960 @default.
- W2004413954 cites W1627088906 @default.
- W2004413954 cites W1629086159 @default.
- W2004413954 cites W171109620 @default.
- W2004413954 cites W1864765563 @default.
- W2004413954 cites W1965541174 @default.
- W2004413954 cites W1966078827 @default.
- W2004413954 cites W1967215274 @default.
- W2004413954 cites W1969244794 @default.
- W2004413954 cites W1972523707 @default.
- W2004413954 cites W1973880590 @default.
- W2004413954 cites W1975224317 @default.
- W2004413954 cites W1980129559 @default.
- W2004413954 cites W1983803126 @default.
- W2004413954 cites W1986191025 @default.
- W2004413954 cites W2002862230 @default.
- W2004413954 cites W2013297186 @default.
- W2004413954 cites W2014814414 @default.
- W2004413954 cites W2015463602 @default.
- W2004413954 cites W2015524830 @default.
- W2004413954 cites W2017523469 @default.
- W2004413954 cites W2029667189 @default.
- W2004413954 cites W2033195419 @default.
- W2004413954 cites W2034675173 @default.
- W2004413954 cites W2036948469 @default.
- W2004413954 cites W2040109036 @default.
- W2004413954 cites W2041372849 @default.
- W2004413954 cites W2042297319 @default.
- W2004413954 cites W2044984191 @default.
- W2004413954 cites W2047594016 @default.
- W2004413954 cites W2047728562 @default.
- W2004413954 cites W2048988573 @default.
- W2004413954 cites W2050706464 @default.
- W2004413954 cites W2059762871 @default.
- W2004413954 cites W2064186318 @default.
- W2004413954 cites W2065283382 @default.
- W2004413954 cites W2065588791 @default.
- W2004413954 cites W2065857393 @default.
- W2004413954 cites W2067102106 @default.
- W2004413954 cites W2072151819 @default.
- W2004413954 cites W2076383259 @default.
- W2004413954 cites W2079163382 @default.
- W2004413954 cites W2080287250 @default.
- W2004413954 cites W2085542201 @default.
- W2004413954 cites W2093381810 @default.
- W2004413954 cites W2096816602 @default.
- W2004413954 cites W2104417933 @default.
- W2004413954 cites W2107020136 @default.
- W2004413954 cites W2107277218 @default.
- W2004413954 cites W2111796184 @default.
- W2004413954 cites W2124851664 @default.
- W2004413954 cites W2127500973 @default.
- W2004413954 cites W2129110633 @default.
- W2004413954 cites W2129300000 @default.
- W2004413954 cites W2129511422 @default.
- W2004413954 cites W2132926880 @default.
- W2004413954 cites W2135328571 @default.
- W2004413954 cites W2137740936 @default.
- W2004413954 cites W2138024978 @default.
- W2004413954 cites W2149809624 @default.
- W2004413954 cites W2151303415 @default.
- W2004413954 cites W2156094132 @default.
- W2004413954 cites W2156631744 @default.
- W2004413954 cites W2156790391 @default.
- W2004413954 cites W2157527374 @default.
- W2004413954 cites W2161453950 @default.
- W2004413954 cites W2162430687 @default.
- W2004413954 cites W2164584173 @default.
- W2004413954 cites W2166052438 @default.
- W2004413954 cites W2169759057 @default.
- W2004413954 cites W2169931873 @default.
- W2004413954 cites W4323966320 @default.
- W2004413954 doi "https://doi.org/10.1016/j.nbd.2011.03.016" @default.
- W2004413954 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21458570" @default.
- W2004413954 hasPublicationYear "2011" @default.
- W2004413954 type Work @default.
- W2004413954 sameAs 2004413954 @default.
- W2004413954 citedByCount "106" @default.
- W2004413954 countsByYear W20044139542012 @default.
- W2004413954 countsByYear W20044139542013 @default.
- W2004413954 countsByYear W20044139542014 @default.