{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:27:50Z","timestamp":1786976870443,"version":"build-2736575974"},"reference-count":16,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"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":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    <jats:italic>DHX16,<\/jats:italic>\n                    a member of the DexD\/H\u2010box RNA helicase family, facilitates ATP\u2010dependent unwinding of RNA secondary structures. Pathogenic variants cause poor functioning of the spliceosome complex leading to intron retention in gene transcripts. Clinically, it is associated with neuromuscular oculoauditory syndrome (MIM #618733). To date, there are nine published cases. We report a tenth case: a 3\u2010year\u2010old female, initially presented at 7\u2009months of age, with mild developmental delay, ocular anomalies, dysmorphia, and increased infections. An inherited retinal disorder panel identified nondiagnostic variants of uncertain significance. Trio exome sequencing revealed a de novo Likely Pathogenic\n                    <jats:italic>DHX16<\/jats:italic>\n                    variant, c.692G&gt;C; p.R231P. Published cases of\n                    <jats:italic>DHX16<\/jats:italic>\n                    \u2010related disorders report developmental delay\/intellectual disability, seizures, myopathy, retinal anomalies, myopia, nystagmus, and hearing loss. No published variants to date are located upstream of the start of the helicase domain, and little is known about upstream domains. In silico analysis demonstrates evidence of pathogenicity, while Missense3D modeling demonstrates no structural damage to the protein. These findings are consistent with current literature, suggesting a mechanism of pathogenicity that is difficult to assess via modeling. This case illustrates a\n                    <jats:italic>DHX16<\/jats:italic>\n                    variant in an unknown domain displaying a mild phenotype.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64083","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T08:09:01Z","timestamp":1746518941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>DHX16\u2010<\/i>\n                    Associated Neuromuscular Oculoauditory Syndrome: A Novel Case"],"prefix":"10.1002","volume":"197","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-7747-9386","authenticated-orcid":false,"given":"Sloane","family":"Clay","sequence":"first","affiliation":[{"name":"Department of Genetics Louisiana State University Health Sciences Center New Orleans  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Leon","sequence":"additional","affiliation":[{"name":"Department of Pediatric Ophthalmology Manning Family Children's  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke A.","family":"Wall","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Division of Allergy and Immunology Louisiana State University Health Sciences Center and Manning Family Children's  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2579-6424","authenticated-orcid":false,"given":"Regina M.","family":"Zambrano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Clinical Genetics Louisiana State University Health Sciences Center and Manning Family Children's  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410\u2010248"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.4103\/aian.aian_67_22"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.63392"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201000141\u20102"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100266"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110434"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.14416"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2019.04.009"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26062812"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.06.001"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.990015"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2011.03.001"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac1052"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23798"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BSR20140142"}],"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.64083","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T09:18:56Z","timestamp":1754903936000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64083"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":16,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/ajmg.a.64083"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64083","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"assertion":[{"value":"2024-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e64083"}}