Feng Haifeng, Xu Hongen, Chen Bei, Sun Shuping, Zhai Rongqun, Zeng Beiping, Tang Wenxue, Lu Wei
Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Center for Applied Precision Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Front Genet. 2021 Nov 15;12:765433. doi: 10.3389/fgene.2021.765433. eCollection 2021.
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. 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 and alterations was performed to explore the genotypes and phenotypes of BOR/BOS-related genes. Genetic testing identified the novel deletion (c.1425delC, p(Asp476Thrfs4); NM_000,503.6), a nonsense variant (c.889C > T, p(Arg297)), and two splicing variants in the gene (c.1050+1G > T and c.1140+1G > A); it also identified one novel missense variant in the gene (c.316G > 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. This is the first report of BOR/BOS caused by the variant in China. Our findings increase the numbers of known and 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.
鳃耳肾综合征（BOR）和鳃耳综合征（BOS）是罕见的常染色体显性疾病，由鳃、耳和肾异常的不同组合所定义。在此，我们对几个中国家庭中BOR/BOS的临床特征和遗传病因进行了表征，然后探索了BOR/BOS相关基因的基因型和表型，以及不同方式听觉康复的结果。先证者和所有受影响的家庭成员均接受了详细的临床检查。对他们的DNA进行全外显子组测序，以探索BOR/BOS的潜在分子病因；候选变异通过桑格测序进行验证，并根据美国医学遗传学学会的指南进行解读。此外，还进行了一项关于[具体基因]改变的文献综述，以探索BOR/BOS相关基因的基因型和表型。基因检测鉴定出了新的缺失（c.1425delC，p(Asp476Thrfs4)；NM_000503.6）、一个无义变异（c.889C>T，p(Arg297)）以及[具体基因]中的两个剪接变异（c.1050+1G>T和c.1140+1G>A）；还在[另一个具体基因]中鉴定出一个新的错义变异（c.316G>A，p(Val106Met)；NM_005982.4）。所有病例在家庭之间或家庭内部均表现出一定程度的表型变异性。改善骨导成分听力损失的中耳手术效果不佳；人工耳蜗植入（CI）有助于听力改善。这是中国首例由[具体基因]变异导致的BOR/BOS报告。我们的发现增加了已知的[具体基因]和[另一个具体基因]变异的数量。它们还强调了基因检测在BOR/BOS诊断和预防中的有用性，同时表明CI用于听觉康复在一些BOR/BOS患者中是一种可行的选择。
