{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:14:05Z","timestamp":1782130445306,"version":"3.54.5"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,7,28]],"date-time":"2015-07-28T00:00:00Z","timestamp":1438041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Pinchas Borenstein Talpiot Medical Leadership Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:p>Two unrelated patients, presenting with significant global developmental delay, severe progressive microcephaly, seizures, spasticity and thin corpus callosum (CC) underwent trio whole\u2010exome sequencing. No candidate variant was found in any known genes related to the phenotype. However, crossing the data of the patients illustrated that they both manifested pathogenic variants in the <jats:italic><jats:styled-content style=\"fixed-case\">SLC1A4<\/jats:styled-content><\/jats:italic> gene which codes the <jats:styled-content style=\"fixed-case\">ASCT1<\/jats:styled-content> transporter of serine and other neutral amino acids. The Ashkenazi patient is homozygous for a deleterious missense c.<jats:styled-content style=\"fixed-case\">766G<\/jats:styled-content>&gt;A, p.(<jats:styled-content style=\"fixed-case\">E256K<\/jats:styled-content>) mutation whereas the Ashkenazi\u2010Iraqi patient is compound heterozygous for this mutation and a nonsense c.<jats:styled-content style=\"fixed-case\">945delTT<\/jats:styled-content>, p.(<jats:styled-content style=\"fixed-case\">Leu315Hisfs<\/jats:styled-content>*42) mutation. Structural prediction demonstrates truncation of significant portion of the protein by the nonsense mutation and speculates functional disruption by the missense mutation. Both mutations are extremely rare in general population databases, however, the missense mutation was found in heterozygous mode in 1:100 Jewish Ashkenazi controls suggesting a higher carrier rate among Ashkenazi Jews. We conclude that <jats:italic><jats:styled-content style=\"fixed-case\">SLC1A4<\/jats:styled-content><\/jats:italic> is the disease causing gene of a novel neurologic disorder manifesting with significant intellectual disability, severe postnatal microcephaly, spasticity and thin CC. The role of <jats:italic><jats:styled-content style=\"fixed-case\">SLC1A4<\/jats:styled-content><\/jats:italic> in the serine transport from astrocytes to neurons suggests a possible pathomechanism for this disease and implies a potential therapeutic approach.<\/jats:p>","DOI":"10.1111\/cge.12637","type":"journal-article","created":{"date-parts":[[2015,7,3]],"date-time":"2015-07-03T15:57:23Z","timestamp":1435939043000},"page":"327-335","source":"Crossref","is-referenced-by-count":56,"title":["<i><scp>SLC1A4<\/scp><\/i> mutations cause a novel disorder of intellectual disability, progressive microcephaly, spasticity and thin corpus callosum"],"prefix":"10.1111","volume":"88","author":[{"given":"G.","family":"Heimer","sequence":"first","affiliation":[{"name":"Pediatric Neurology Unit Edmond and Lily Safra Children's Hospital  Ramat Gan Israel"},{"name":"The Pinchas Borenstein Talpiot Medical Leadership Program  Ramat Gan 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