{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T18:27:58Z","timestamp":1790015278973,"version":"4.0.1"},"reference-count":59,"publisher":"Cold Spring Harbor Laboratory","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:p>Hearing loss (HL) is the most common congenital sensory impairment. Usher syndrome (USH) is the leading genetic etiology of congenital deafness combined with progressive vision loss, and individuals presenting with these symptoms are often assumed to have USH. This can be an erroneous assumption, as there are additional genetic causes of deaf-blindness. Our objective is to describe and accurately diagnose non-USH genetic causes of deaf-blindness. We present three children with hearing and vision loss with clinical and genetic findings suggestive of USH. However, ongoing clinical assessment did not completely support an USH diagnosis, and exome analysis was pursued for all three individuals. Updated genetic testing showed pathogenic variants in <jats:italic>ALMS1<\/jats:italic> in the first individual and <jats:italic>TUBB4B<\/jats:italic> in the second and third. Although HL in all three was consistent with USH type 2, vision impairment with retinal changes was noted by age 2 yr, which is unusual for USH. In all three the updated genotype more accurately fit the clinical phenotype. Because USH is the most common form of genetic deaf-blindness, individuals with HL, early vision impairment, and retinal dysfunction are often assumed to have USH. However, additional genes associated with HL and retinal impairment include <jats:italic>ALMS1<\/jats:italic>, <jats:italic>TUBB4B<\/jats:italic>, <jats:italic>CEP78<\/jats:italic>, <jats:italic>ABHD12<\/jats:italic>, and <jats:italic>PRPS1<\/jats:italic>. Accurate genetic diagnosis is critical to these individuals\u2019 understanding of their genetic conditions, prognosis, vision and hearing loss management, and future access to molecular therapies. If clinically or genetically USH seems uncertain, updated genetic testing for non-USH genes is essential.<\/jats:p>","DOI":"10.1101\/mcs.a006088","type":"journal-article","created":{"date-parts":[[2021,5,21]],"date-time":"2021-05-21T18:30:19Z","timestamp":1621621819000},"page":"a006088","source":"Crossref","is-referenced-by-count":11,"title":["Hiding in plain sight: genetic deaf-blindness is not always Usher syndrome"],"prefix":"10.1101","volume":"7","author":[{"given":"Genevieve","family":"Medina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Perry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Oza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret","family":"Kenna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"2021112506233781000_7.4.a006088.1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-014-0190-9"},{"key":"2021112506233781000_7.4.a006088.2","first-page":"1","article-title":"Retinal degeneration combined with obesity, diabetes mellitus and neurogenous deafness: a specific syndrome (not hitherto described) distinct from the Laurence\u2013Moon\u2013Bardet\u2013Biedl syndrome: a clinical, endocrinological and genetic examination based on a large pedigree","volume":"125","year":"1959","journal-title":"Acta Psychiatr Neurol Scand"},{"key":"2021112506233781000_7.4.a006088.3","doi-asserted-by":"publisher","DOI":"10.1353\/aad.2016.0034"},{"key":"2021112506233781000_7.4.a006088.4","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410330519"},{"key":"2021112506233781000_7.4.a006088.5","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23233"},{"key":"2021112506233781000_7.4.a006088.6","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34071"},{"key":"2021112506233781000_7.4.a006088.7","doi-asserted-by":"publisher","DOI":"10.3109\/13816819609057892"},{"key":"2021112506233781000_7.4.a006088.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0272-6386(98)70083-6"},{"key":"2021112506233781000_7.4.a006088.9","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.76.3.171"},{"key":"2021112506233781000_7.4.a006088.10","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12196"},{"key":"2021112506233781000_7.4.a006088.11","doi-asserted-by":"publisher","DOI":"10.3109\/14992020903311388"},{"key":"2021112506233781000_7.4.a006088.12","unstructured":"de Brouwer APM , Christodoulou J . 2018. 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