{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:06:07Z","timestamp":1790787967714,"version":"4.1.0"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T00:00:00Z","timestamp":1618272000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009633","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P50HD103555"],"award-info":[{"award-number":["P50HD103555"]}],"id":[{"id":"10.13039\/100009633","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["HICF\u20101009\u2010003"],"award-info":[{"award-number":["HICF\u20101009\u2010003"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000052","name":"NIH Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000052","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006086","name":"Office of Strategic Coordination","doi-asserted-by":"publisher","award":["U01HG007709"],"award-info":[{"award-number":["U01HG007709"]}],"id":[{"id":"10.13039\/100006086","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spectrins are common components of cytoskeletons, binding to cytoskeletal elements and the plasma membrane, allowing proper localization of essential membrane proteins, signal transduction, and cellular scaffolding. Spectrins are assembled from \u03b1 and \u03b2 subunits, encoded by <jats:italic>SPTA1<\/jats:italic> and <jats:italic>SPTAN1<\/jats:italic> (\u03b1) and <jats:italic>SPTB<\/jats:italic>, <jats:italic>SPTBN1<\/jats:italic>, <jats:italic>SPTBN2<\/jats:italic>, <jats:italic>SPTBN4<\/jats:italic>, and <jats:italic>SPTBN5<\/jats:italic> (\u03b2). Pathogenic variants in various spectrin genes are associated with erythroid cell disorders (<jats:italic>SPTA1<\/jats:italic>, <jats:italic>SPTB<\/jats:italic>) and neurologic disorders (<jats:italic>SPTAN1<\/jats:italic>, <jats:italic>SPTBN2<\/jats:italic>, and <jats:italic>SPTBN4<\/jats:italic>), but no phenotypes have been definitively associated with variants in <jats:italic>SPTBN1<\/jats:italic> or <jats:italic>SPTBN5<\/jats:italic>. Through exome sequencing and case matching, we identified seven unrelated individuals with heterozygous <jats:italic>SPTBN1<\/jats:italic> variants: two with de novo missense variants and five with predicted loss\u2010of\u2010function variants (found to be de novo in two, while one was inherited from a mother with a history of learning disabilities). Common features include global developmental delays, intellectual disability, and behavioral disturbances. Autistic features (4\/6) and epilepsy (2\/7) or abnormal electroencephalogram without overt seizures (1\/7) were present in a subset. Identification of loss\u2010of\u2010function variants suggests a haploinsufficiency mechanism, but additional functional studies are required to fully elucidate disease pathogenesis. Our findings support the essential roles of <jats:italic>SPTBN1<\/jats:italic> in human neurodevelopment and expand the knowledge of human spectrinopathy disorders.<\/jats:p>","DOI":"10.1002\/ajmg.a.62201","type":"journal-article","created":{"date-parts":[[2021,4,13]],"date-time":"2021-04-13T22:34:27Z","timestamp":1618353267000},"page":"2037-2045","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Heterozygous variants in <i>SPTBN1<\/i> cause intellectual disability and autism"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5664-7987","authenticated-orcid":false,"given":"Jill A.","family":"Rosenfeld","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics Laboratories  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mir Reza","family":"Bekheirnia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Renal Section, Department of Pediatrics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farah","family":"Kanani","sequence":"additional","affiliation":[{"name":"Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Parker","sequence":"additional","affiliation":[{"name":"Sheffield Clinical Genetics Service, Sheffield Children's NHS Foundation Trust  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary K.","family":"Koenig","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Texas McGovern Medical School  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie","family":"van Haeringen","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Ruivenkamp","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Leiden University Medical Center  Leiden Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Rosmaninho\u2010Salgado","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Hospital Pedi\u00e1trico, Centro Hospitalar e Universit\u00e1rio de Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro M.","family":"Almeida","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Hospital Pedi\u00e1trico, Centro Hospitalar e Universit\u00e1rio de Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquim","family":"S\u00e1","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Hospital Pedi\u00e1trico, Centro Hospitalar e Universit\u00e1rio de Coimbra  Coimbra Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Pinto Basto","sequence":"additional","affiliation":[{"name":"Molecular Diagnostics and Clinical Genomics, CGC Genetics  Porto Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Palen","sequence":"additional","affiliation":[{"name":"Autism &amp; Developmental Medicine Institute, Geisinger  Danville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn F.","family":"Oetjens","sequence":"additional","affiliation":[{"name":"Autism &amp; Developmental Medicine Institute, Geisinger  Danville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5108-8861","authenticated-orcid":false,"given":"Lindsay C.","family":"Burrage","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fan","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics Laboratories  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4177-709X","authenticated-orcid":false,"given":"Pengfei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics Laboratories  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Eng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics Laboratories  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Undiagnosed Diseases Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Baylor Genetics Laboratories  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4814-6765","authenticated-orcid":false,"given":"Jennifer E.","family":"Posey","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan H.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1843-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.95.2.478"},{"key":"e_1_2_9_4_1","volume-title":"The National Genomics Research and healthcare knowledgebase v5","author":"Caulfield M.","year":"2019"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI80937"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1132"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi991458k"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq279"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809245200"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature14135"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.11.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0005-2736(03)00032-4"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2013.150"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2009.03.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.039"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/bcmd.1996.0105"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119155"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117766"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(83)90383-5"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.271"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.11.2023"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1728"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13908"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-017-1814-7"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2012.06.143"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018259"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003074"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2013.05.002"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113047"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.159.3811.203"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13185"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.04.008"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.05.015"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky300"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2010.04.013"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-8993(99)02253-2"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013708"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3647-17.2018"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1075994"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0293-0"},{"key":"e_1_2_9_42_1","volume-title":"GeneReviews","author":"Vergano S. S.","year":"2013"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.04.012"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.14601"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.162347"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62201","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62201","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62201","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:43:23Z","timestamp":1692953003000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62201"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,13]]},"references-count":44,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/ajmg.a.62201"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62201","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,13]]},"assertion":[{"value":"2020-09-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}