{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T12:14:08Z","timestamp":1782130448180,"version":"3.54.5"},"reference-count":10,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,5,28]],"date-time":"2015-05-28T00:00:00Z","timestamp":1432771200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Jean-Louis Levesque"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2015,7]]},"abstract":"We performed exome analysis in two affected siblings with severe intellectual disability (ID<\/jats:styled-content>), microcephaly and spasticity from an Ashkenazi Jewish consanguineous family. We identified only one rare variant, a missense in SLC1A4<\/jats:styled-content><\/jats:italic> (c. 766G<\/jats:styled-content>>A [p. E256K<\/jats:styled-content>]), that is homozygous in both siblings but not in any of their 11 unaffected siblings or their parents (Logarithm of odds, LOD<\/jats:styled-content> score: 2.6). This variant is predicted damaging. We genotyped 450 controls of Ashkenazi Jewish ancestry and identified only 5 individuals who are heterozygous for this variant (minor allele frequency: 0.0056). SLC1A4<\/jats:styled-content><\/jats:italic> (ASCT1<\/jats:styled-content>) encodes a transporter for neutral aminoacids such as alanine, serine, cysteine and threonine. l<\/jats:sc>\u2010Serine is essential for neuronal survival and differentiation. Indeed, l<\/jats:sc>\u2010serine biosynthesis disorders affect brain development and cause severe ID<\/jats:styled-content>. In the brain, l<\/jats:sc>\u2010serine is synthesized in astrocytes but not in neurons. It has been proposed that ASCT1<\/jats:styled-content> mediates the uptake of l<\/jats:sc>\u2010serine into neurons and the release of glia\u2010borne l<\/jats:sc>\u2010serine to neighboring cells. SLC1A4<\/jats:styled-content><\/jats:italic> disruption may thus impair brain development and function by decreasing the levels of l<\/jats:sc>\u2010serine in neurons. The identification of additional families with mutations in SLC1A4<\/jats:styled-content><\/jats:italic> would be necessary to confirm its involvement in ID<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/cge.12605","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T14:46:56Z","timestamp":1430405216000},"source":"Crossref","is-referenced-by-count":48,"title":["A homozygous mutation in SLC1A4<\/scp><\/i> in siblings with severe intellectual disability and microcephaly"],"prefix":"10.1111","volume":"88","author":[{"given":"M.","family":"Srour","sequence":"first","affiliation":[{"name":"Division of Pediatric Neurology Montreal Children's Hospital, McGill University Health Center Montreal Canada"},{"name":"CHU Sainte\u2010Justine Research Center Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. F.","family":"Hamdan","sequence":"additional","affiliation":[{"name":"CHU Sainte\u2010Justine Research Center Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Z.","family":"Gan\u2010Or","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute McGill University Montreal H3A 2B4 Canada"},{"name":"Department of Human Genetics McGill University Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Labuda","sequence":"additional","affiliation":[{"name":"CHU Sainte\u2010Justine Research Center Montreal Canada"},{"name":"Department of Pediatrics Universit\u00e9 de Montr\u00e9al Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Nassif","sequence":"additional","affiliation":[{"name":"CHU Sainte\u2010Justine Research Center Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Oskoui","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology Montreal Children's Hospital, McGill University Health Center Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Gana\u2010Weisz","sequence":"additional","affiliation":[{"name":"The Genetic Institute Tel\u2010Aviv Sourasky Medical Center Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Orr\u2010Urtreger","sequence":"additional","affiliation":[{"name":"The Genetic Institute Tel\u2010Aviv Sourasky Medical Center Tel\u2010Aviv Israel"},{"name":"Sackler Faculty of Medicine Tel\u2010Aviv University Tel\u2010Aviv Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.A.","family":"Rouleau","sequence":"additional","affiliation":[{"name":"Montreal Neurological Institute McGill University Montreal H3A 2B4 Canada"},{"name":"Department of Human Genetics McGill University Montreal Canada"},{"name":"Department of Neurology and Neurosurgery McGill University Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.L.","family":"Michaud","sequence":"additional","affiliation":[{"name":"CHU Sainte\u2010Justine Research Center Montreal Canada"},{"name":"Department of Pediatrics Universit\u00e9 de Montr\u00e9al Montreal Canada"},{"name":"Department of Neurosciences Universit\u00e9 de Montr\u00e9al Montreal Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,28]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000277637.33328.d8"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-0102(97)00113-2"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1679\/aohc.66.109"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-19-07691.2001"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00742-7"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2004.02.004"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.200364497"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-02-00550.2003"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-3806(01)00250-4"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2009.10.012"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcge.12605","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.12605","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T06:42:22Z","timestamp":1696315342000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.12605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5,28]]},"references-count":10,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,7]]}},"alternative-id":["10.1111\/cge.12605"],"URL":"https:\/\/doi.org\/10.1111\/cge.12605","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5,28]]}}}