{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:29:20Z","timestamp":1790710160515,"version":"4.1.0"},"reference-count":24,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T00:00:00Z","timestamp":1656115200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005202","name":"Muscular Dystrophy Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005202","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","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":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Joubert syndrome (JS), a well\u2010established ciliopathy, is characterized by the distinctive molar tooth sign on brain MRI, ataxia, and neurodevelopmental features. Other manifestations can include polydactyly, accessory frenula, renal, or liver disease. Here, we report individuals meeting criteria for JS with <jats:italic>de novo<\/jats:italic> heterozygous variants in <jats:italic>SLC30A7<\/jats:italic> (Chr1p21.2). The first individual is a female with history of unilateral postaxial polydactyly, classic molar tooth sign on MRI, macrocephaly, ataxia, ocular motor apraxia, neurodevelopmental delay, and precocious puberty. Exome sequencing detected a <jats:italic>de novo<\/jats:italic> heterozygous missense variant in <jats:italic>SLC30A7<\/jats:italic>: NM_133496.5: c.407\u2009T\u2009&gt;\u2009C, (p.Val136Ala). The second individual had bilateral postaxial polydactyly, molar tooth sign, macrocephaly, developmental delay, and an extra oral frenulum. A <jats:italic>de novo<\/jats:italic> deletion\u2013insertion variant in <jats:italic>SLC30A7<\/jats:italic>, c.490_491delinsAG (p.His164Ser) was found. Both <jats:italic>de novo<\/jats:italic> variants affect highly conserved residues. Variants were not identified in known Joubert genes for either case. <jats:italic>SLC30A7<\/jats:italic> has not yet been associated with a human phenotype. The SLC30 family of zinc transporters, like SLC30A7, permit cellular efflux of zinc, and although it is expressed in the brain its functions remain unknown. Published data from proteomic studies support SLC30A7 interaction with TCTN3, another protein associated with JS. The potential involvement of such genes in primary cilia suggest a role in Sonic Hedgehog signaling. <jats:italic>SLC30A7<\/jats:italic> is a candidate JS\u2010associated gene. Future work could be directed toward further characterization of <jats:italic>SLC30A7<\/jats:italic> variants and understanding its function.<\/jats:p>","DOI":"10.1002\/ajmg.a.62872","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T07:08:43Z","timestamp":1656140923000},"page":"2360-2366","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>De novo<\/i> heterozygous variants in <scp><i>SLC30A7<\/i><\/scp> are a candidate cause for Joubert syndrome"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3011-440X","authenticated-orcid":false,"given":"Monica","family":"Penon\u2010Portmann","sequence":"first","affiliation":[{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad K.","family":"Eldomery","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Potocki","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2233-3423","authenticated-orcid":false,"given":"Dana","family":"Marafi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  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":"Zeynep","family":"Coban\u2010Akdemir","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genetics Center, Department of Epidemiology Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3595-7075","authenticated-orcid":false,"given":"Tamar","family":"Harel","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Grochowski","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailey","family":"Loucks","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Washington  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter Patrick","family":"Devine","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Van Ziffle","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9377-028X","authenticated-orcid":false,"given":"Dan","family":"Doherty","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Washington  Seattle WA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9907-9246","authenticated-orcid":false,"given":"James R.","family":"Lupski","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"},{"name":"Department of Pediatrics Baylor College of Medicine  Houston Texas USA"},{"name":"Human Genome Sequencing Center Baylor College of Medicine  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0746-6084","authenticated-orcid":false,"given":"Joseph T.","family":"Shieh","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103087"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61399"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3182106775"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41390-020-01181-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62192"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-017-0412-6"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjgenmed.2016.36"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.09.027"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.05.008"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.14670\/HH-24.567"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2892"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207644200"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab369"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61450"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3233\/trd-190041"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.252601.119"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1363606"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70136-4"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-016-1099-5"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz457"},{"key":"e_1_2_9_23_1","doi-asserted-by":"crossref","unstructured":"Sobreira N. Schiettecatte F. Valle D. &Hamosh A.(2015).GeneMatcher: A matching tool for connecting investigators with an interest in the same gene.Human Mutation 36(10) 928\u2013930.https:\/\/doi.org\/10.1002\/humu.22844","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12438-5"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2020.100016.TMEM218"}],"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.62872","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62872","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62872","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T06:15:52Z","timestamp":1692857752000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,25]]},"references-count":24,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/ajmg.a.62872"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62872","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,25]]},"assertion":[{"value":"2022-04-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}