{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:36:11Z","timestamp":1780493771403,"version":"3.54.1"},"reference-count":16,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"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":[[2021,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The heterozygous deletion of 15q13.3 is a recurrently observed microdeletion syndrome associated with a relatively mild phenotype including learning disability and language impairment. In contrast, the homozygous deletion of 15q13.3 is extremely rare and is associated with a much severer phenotype that includes epileptic encephalopathy, profound intellectual disability, and hypotonia. Which of the genes within the deleted interval is responsible for the more severe features when biallelically deleted is currently unknown. Here, we report a patient with profound hypotonia, severe intellectual disability, and seizures who had biallelic loss\u2010of\u2010function variants in <jats:italic>OTUD7A<\/jats:italic>: a 15q13.3 deletion including the <jats:italic>OTUD7A<\/jats:italic> locus, and a frameshift <jats:italic>OTUD7A<\/jats:italic> variant c.1125del, p.(Glu375Aspfs*11). Unexpectedly, both aberrations occurred de novo. Our experiment using <jats:italic>Caenorhabditis elegans<\/jats:italic> showed that worms carrying a corresponding homozygous variant in the homolog OTUB\u20102 exhibited weakened muscle contraction suggestive of aberrant neuromuscular transmission. We concluded that the biallelic complete loss of <jats:italic>OTUD7A<\/jats:italic> in humans represents a presumably new autosomal recessive disorder characterized by profound hypotonia, severe intellectual disability, and seizures.<\/jats:p>","DOI":"10.1002\/ajmg.a.62054","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T08:54:53Z","timestamp":1609404893000},"page":"1182-1186","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Biallelic loss of <i>OTUD7A<\/i> causes severe muscular hypotonia, intellectual disability, and seizures"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8122-7180","authenticated-orcid":false,"given":"Hisato","family":"Suzuki","sequence":"first","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine  Tokyo 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