{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:41:48Z","timestamp":1789144908890,"version":"build-2803163510"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T00:00:00Z","timestamp":1684972800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp; Gen Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Usher syndrome is a condition characterized by partial or total hearing loss and progressive pigmentary retinopathy. Usher syndrome type 1F is caused by biallelic loss\u2010of\u2010function variants in Protocadherin 15 (<jats:italic>PCDH15<\/jats:italic>), which encodes the PCDH15 protein that plays an important role in the morphogenesis and cohesion of stereocilium bundles and retinal photoreceptor cell maintenance and function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report a child with bilateral nonsyndromic sensorineural hearing loss who received an inconclusive diagnosis based on clinical gene panel testing, which identified a paternal heterozygous nonsense variant (NM_033056.4: c.733C&gt;T, p.R245*) in <jats:italic>PCDH15<\/jats:italic>. This variant has been described as a founder variant in the Ashkenazi Jewish population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A novel deep\u2010intronic variant (NM_033056.4: c.705+3767_705+3768del) inherited from the patient's mother was identified by trio\u2010based whole\u2010genome sequencing (WGS). A minigene splicing assay revealed that c.705+3767_705+3768del results in aberrant retention of 50 or 68\u2009bp of intron 7.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our genetic test results provided precise genetic counseling and prenatal diagnosis for this family, and our findings highlight the power of WGS for detecting deep\u2010intronic variants in patients with undiagnosed rare diseases. Additionally, this case expands the variant spectrum of the <jats:italic>PCDH15<\/jats:italic> gene and our results support the extremely low carrier frequency of c.733C&gt;T in the Chinese population.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2193","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T05:41:48Z","timestamp":1685079708000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Case report: Compound heterozygous nonsense <scp><i>PCDH15<\/i><\/scp> variant and a novel deep\u2010intronic variant in a Chinese child with profound hearing loss"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0370-958X","authenticated-orcid":false,"given":"Ziying","family":"Yang","sequence":"first","affiliation":[{"name":"College of Life Sciences University of Chinese Academy of Sciences  Beijing China"},{"name":"Tianjin Medical Laboratory, BGI\u2010Tianjin, 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