{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:14:53Z","timestamp":1787026493582,"version":"build-2736575974"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Branchio-oto-renal syndrome (BOR) and branchio-oto syndrome (BOS) are rare autosomal dominant disorders defined by varying combinations of branchial, otic, and renal anomalies. Here, we characterized the clinical features and genetic etiology of BOR\/BOS in several Chinese families and then explored the genotypes and phenotypes of BOR\/BOS-related genes, as well as the outcomes of auditory rehabilitation in different modalities.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Materials and Methods:<\/jats:bold>\n                    Probands and all affected family members underwent detailed clinical examinations. Their DNA was subjected to whole-exome sequencing to explore the underlying molecular etiology of BOR\/BOS; candidate variants were validated using Sanger sequencing and interpreted in accordance with the American College of Medical Genetics guidelines. In addition, a literature review concerning\n                    <jats:italic>EYA1<\/jats:italic>\n                    and\n                    <jats:italic>SIX1<\/jats:italic>\n                    alterations was performed to explore the genotypes and phenotypes of BOR\/BOS-related genes.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Genetic testing identified the novel deletion (c.1425delC, p(Asp476Thrfs*4); NM_000,503.6), a nonsense variant (c.889C &amp;gt; T, p(Arg297*)), and two splicing variants in the\n                    <jats:italic>EYA1<\/jats:italic>\n                    gene (c.1050+1G &amp;gt; T and c.1140+1G &amp;gt; A); it also identified one novel missense variant in the\n                    <jats:italic>SIX1<\/jats:italic>\n                    gene (c.316G &amp;gt; A, p(Val106Met); NM_005,982.4). All cases exhibited a degree of phenotypic variability between or within families. Middle ear surgeries for improving bone-conduction component hearing loss had unsuccessful outcomes; cochlear implantation (CI) contributed to hearing gains.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    This is the first report of BOR\/BOS caused by the\n                    <jats:italic>SIX1<\/jats:italic>\n                    variant in China. Our findings increase the numbers of known\n                    <jats:italic>EYA1<\/jats:italic>\n                    and\n                    <jats:italic>SIX1<\/jats:italic>\n                    variants. They also emphasize the usefulness of genetic testing in the diagnosis and prevention of BOR\/BOS while demonstrating that CI for auditory rehabilitation is a feasible option in some BOR\/BOS patients.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2021.765433","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T07:10:03Z","timestamp":1636960203000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Genetic and Phenotypic Variability in Chinese Patients With Branchio-Oto-Renal or Branchio-Oto Syndrome"],"prefix":"10.3389","volume":"12","author":[{"given":"Haifeng","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuping","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongqun","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiping","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxue","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1038\/ng0297-157","article-title":"A Human Homologue of the Drosophila Eyes Absent Gene Underlies Branchio-Oto-Renal (BOR) Syndrome and Identifies a Novel Gene Family","volume":"15","author":"Abdelhak","year":"1997","journal-title":"Nat. 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