AUTHOR=Feng Haifeng , Xu Hongen , Chen Bei , Sun Shuping , Zhai Rongqun , Zeng Beiping , Tang Wenxue , Lu Wei 

TITLE=Genetic and Phenotypic Variability in Chinese Patients With Branchio-Oto-Renal or Branchio-Oto Syndrome

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.765433

DOI=10.3389/fgene.2021.765433

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Materials and Methods:</bold> 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 <italic>EYA1</italic> and <italic>SIX1</italic> alterations was performed to explore the genotypes and phenotypes of BOR/BOS-related genes.</p><p><bold>Results:</bold> Genetic testing identified the novel deletion (c.1425delC, p(Asp476Thrfs*4); NM_000,503.6), a nonsense variant (c.889C &gt; T, p(Arg297*)), and two splicing variants in the <italic>EYA1</italic> gene (c.1050+1G &gt; T and c.1140+1G &gt; A); it also identified one novel missense variant in the <italic>SIX1</italic> gene (c.316G &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.</p><p><bold>Conclusion:</bold> This is the first report of BOR/BOS caused by the <italic>SIX1</italic> variant in China. Our findings increase the numbers of known <italic>EYA1</italic> and <italic>SIX1</italic> 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.</p>