{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T20:33:06Z","timestamp":1779395586581,"version":"3.53.1"},"reference-count":41,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,12,11]],"date-time":"2019-12-11T00:00:00Z","timestamp":1576022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sorting nexin 27 (SNX27) influences the composition of the cellular membrane via regulation of selective endosomal recycling. Molecular analysis indicates that SNX27 regulates numerous cellular processes through promiscuous interactions with its receptor cargos. <jats:italic>SNX27<\/jats:italic> deficient (<jats:italic>Snx27<\/jats:italic><jats:sup>\n<jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) mice exhibit reduced embryonic survival, marked postnatal growth restriction and lethality. Haploinsufficient mice (<jats:italic>Snx27<\/jats:italic><jats:sup>\n<jats:italic>+\/\u2212<\/jats:italic><\/jats:sup>) show a less severe phenotype, with deficits in learning, memory, synaptic transmission and neuronal plasticity. One family previously reported with a homozygous <jats:italic>SNX27<\/jats:italic> frameshift variant (c.515_516del;p.His172Argfs*6), exhibited infantile intractable myoclonic epilepsy, axial hypotonia, startle\u2010like movements, cardiac septal defects, global developmental delay, failure to thrive, recurrent chest infections, persistent hypoxemia and early death secondary to respiratory failure. Here, we report two additional patients with compound heterozygous <jats:italic>SNX27<\/jats:italic> variants, that are predicted to be damaging: (a) c.510C&gt;G;p.Tyr170* and c.1295G&gt;A;p.Cys432Tyr, and (b) c.782dupT;p.Leu262Profs*6 and c.989G&gt;A;p.Arg330His. They exhibit global developmental delay, behavioral disturbance, epilepsy, some dysmorphic features and subcortical white matter abnormalities. In addition, possible connective tissue involvement was noted. Epilepsy, developmental delays and subcortical white matter abnormalities appear to be core features of <jats:italic>SNX27<\/jats:italic>\u2010related disorders. We correlate the observed phenotype with available in vitro, in vivo and proteomic data and suggest additional possible molecular mediators of <jats:italic>SNX27<\/jats:italic>\u2010related pathology.<\/jats:p>","DOI":"10.1111\/cge.13675","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T15:56:21Z","timestamp":1573660581000},"page":"437-446","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Sorting nexin 27 (<i>SNX27<\/i>) variants associated with seizures, developmental delay, behavioral disturbance, and subcortical brain abnormalities"],"prefix":"10.1111","volume":"97","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7990-4576","authenticated-orcid":false,"given":"Daniel J.","family":"Parente","sequence":"first","affiliation":[{"name":"Department of Family Medicine University of Kansas Medical Center  Kansas City Kansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie M.","family":"Morris","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"McKinstry","sequence":"additional","affiliation":[{"name":"Pediatric Radiology and Pediatric Neuroradiology, Mallinckrodt Institute of Radiology Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracy","family":"Brandt","sequence":"additional","affiliation":[{"name":"GeneDx  Gaithersburg Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Gabau","sequence":"additional","affiliation":[{"name":"Paediatric Unit, Parc Taul\u00ed Hospital Universitari, Institut d'Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed I3PT Universitat Aut\u00f2noma de Barcelona  Sabadell Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7314-5962","authenticated-orcid":false,"given":"Anna","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, UDIAT\u2010Centre Diagn\u00f2stic, Parc Taul\u00ed Hospital Universitari, Institut d'Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed I3PT Universitat Aut\u00f2noma de Barcelona  Sabadell Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1329-4100","authenticated-orcid":false,"given":"Marwan","family":"Shinawi","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomic Medicine, Department of Pediatrics Washington University School of Medicine  St. Louis Missouri"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059800"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1412415111"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.O112.021022"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2587-15.2015"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.10220"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01379"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.158204"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.337931"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01499-15"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.260802"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E14-12-1597"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20150205"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.10.053"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01044-10"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2721"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1410552111"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1017110108"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3117"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1620-16.2016"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-015-0446-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv195"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1016"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22225"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19113581"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4176"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep38321"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5563"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep37033"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22266"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2017-223858"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2013.07.003"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000046"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37977"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt283"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201701-0134OC"},{"key":"e_1_2_8_41_1","first-page":"304717","article-title":"Sorting Nexin 27 (SNX27): a novel regulator of cystic fibrosis Transmembrane conductance regulator (CFTR) trafficking","author":"McDermott MI","year":"2018","journal-title":"bioRxiv"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201206028"}],"container-title":["Clinical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13675","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cge.13675","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cge.13675","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,7]],"date-time":"2023-09-07T01:10:10Z","timestamp":1694049010000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cge.13675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,11]]},"references-count":41,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2020,3]]}},"alternative-id":["10.1111\/cge.13675"],"URL":"https:\/\/doi.org\/10.1111\/cge.13675","archive":["Portico"],"relation":{},"ISSN":["0009-9163","1399-0004"],"issn-type":[{"value":"0009-9163","type":"print"},{"value":"1399-0004","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,11]]},"assertion":[{"value":"2019-07-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-11-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-12-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}