{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T04:55:10Z","timestamp":1758862510451,"version":"3.40.5"},"reference-count":4,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,20]],"date-time":"2020-10-20T00:00:00Z","timestamp":1603152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17ek0109281"],"award-info":[{"award-number":["JP17ek0109281"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","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":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The <jats:italic>NSUN2<\/jats:italic> gene encodes a tRNA cytosine methyltransferase that functions in the maturation of leucyl tRNA (Leu) (CAA) precursors, which is crucial for the anticodon\u2010codon pairing and correct translation of mRNA. Biallelic loss of function variants in <jats:italic>NSUN2<\/jats:italic> are known to cause moderate to severe intellectual disability. Microcephaly, postnatal growth retardation, and dysmorphic facial features are common complications in this genetic disorder, and delayed puberty is occasionally observed. Here, we report four individuals, two sets of siblings, with biallelic loss\u2010of\u2010function variants in the <jats:italic>NSUN2<\/jats:italic> gene. The first set of siblings have compound heterozygous frameshift variants: c.546_547insCT, p.Met183Leufs*13; c.1583del, p.Pro528Hisfs*19, and the other siblings carry a homozygous frameshift variant: c.1269dup, p.Val424Cysfs*14. In addition to previously reported clinical features, the first set of siblings showed novel complications of juvenile cataract and chronic nephritis. The other siblings showed hypomyelination and simplified gyral pattern in neuroimaging. <jats:italic>NSUN2<\/jats:italic>\u2010related intellectual disability is a very rare condition, and less than 20 cases have been reported previously. Juvenile cataract, chronic nephritis, and brain anomaly shown in the present patients have not been previously described. Our report suggests clinical diversity of <jats:italic>NSUN2<\/jats:italic>\u2010related intellectual disability.<\/jats:p>","DOI":"10.1002\/ajmg.a.61927","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T07:03:35Z","timestamp":1603263815000},"page":"282-285","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Expanding the phenotype of biallelic loss\u2010of\u2010function variants in the <scp><i>NSUN2<\/i><\/scp> gene: Description of four individuals with juvenile cataract, chronic nephritis, or brain anomaly as novel complications"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5704-2936","authenticated-orcid":false,"given":"Kohji","family":"Kato","sequence":"first","affiliation":[{"name":"Department of Genetics, Research Institute of Environmental Medicine Nagoya University  Nagoya Japan"},{"name":"Department of Pediatrics Central Hospital, Aichi Human Service Center  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seiji","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Central Hospital, Aichi Human Service Center  Aichi Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenny","family":"Morton","sequence":"additional","affiliation":[{"name":"West Midlands Regional Clinical Genetics Service and Birmingham Health Partners Birmingham Women's and Children's Hospitals NHS Foundation Trust  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miho","family":"Toyama","sequence":"additional","affiliation":[{"name":"Department of Genetics, Research Institute of Environmental Medicine Nagoya University  Nagoya Japan"},{"name":"Department of Psychiatry Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuichiro","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Genetics, Research Institute of Environmental Medicine Nagoya University  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evangeline","family":"Wasmer","sequence":"additional","affiliation":[{"name":"Department of Neurology and Genetics Birmingham Women's and Children's Hospital, NHS Foundation Trust  Birmingham UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Lehmann","sequence":"additional","affiliation":[{"name":"Genome Damage and Stability Centre University of Sussex  Brighton UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5492-9072","authenticated-orcid":false,"given":"Tomoo","family":"Ogi","sequence":"additional","affiliation":[{"name":"Department of Genetics, Research Institute of Environmental Medicine Nagoya University  Nagoya Japan"},{"name":"Department of Human Genetics and Molecular Biology Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,10,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.03.021"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.015263"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40489"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.03.023"}],"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.61927","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.61927","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.61927","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T07:04:32Z","timestamp":1693811072000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.61927"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,20]]},"references-count":4,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1]]}},"alternative-id":["10.1002\/ajmg.a.61927"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.61927","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"type":"print","value":"1552-4825"},{"type":"electronic","value":"1552-4833"}],"subject":[],"published":{"date-parts":[[2020,10,20]]},"assertion":[{"value":"2020-07-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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