Department of Otolaryngology-Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha 410008.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China.
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2022 Jan 28;47(1):129-138. doi: 10.11817/j.issn.1672-7347.2022.210251.
Branchio-oto syndrome (BOS)/branchio-oto-renal syndrome (BORS) is a kind of autosomal dominant heterogeneous disorder. These diseases are mainly characterized by hearing impairment and abnormal phenotype of ears, accompanied by renal malformation and branchial cleft anomalies including cyst or fistula, with an incidence of 1/40 000 in human population. Otic anormalies are one of the most obvious clinical manifestations of BOS/BORS, including deformities of external, middle, inner ears and hearing loss with conductive, sensorineural or mix, ranging from mild to profound loss. Temporal bone imaging could assist in the diagnosis of middle ear and inner ear malformations for clinicians. Multiple methods including direct sequencing combined with next generation sequencing (NGS), multiplex ligation-dependent probe amplification (MLPA), or array-based comparative genomic hybridization (aCGH) can effectively screen and identify pathogenic genes and/or variation types of BOS/BORS. About 40% of patients with BOS/BORS carry aberrations of gene which is the most important cause of BOS/BORS. A total of 240 kinds of pathogenic variations of have been reported in different populations so far, including frameshift, nonsense, missense, aberrant splicing, deletion and complex rearrangements. Human Endogenous Retroviral sequences (HERVs) may play an important role in mediating chromosomal fragment deletion mutations caused by non-allelic homologous recombination. encodes a phosphatase-transactivator cooperated with transcription factors of , participates in cranial sensory neurogenesis and development of branchial arch-derived organs, then regulates the morphological and functional differentiation of the outer ear, middle ear and inner ear toward normal tissues. In addition, pathogenic mutations of and genes can also cause BOS/BORS. Variations of these genes mentioned above may cause disease by destroying the bindings between SIX1-EYA1, SIX5-EYA1 or SIX1-DNA. However, the role of gene in the pathogenesis of BORS needs further verification.
并指-耳-肾综合征（BOS）/并指-耳-肾-眼综合征（BORS）是一种常染色体显性遗传的异质性疾病。这些疾病主要表现为听力障碍和耳部异常表型，伴有肾畸形和鳃裂异常，包括囊肿或瘘管，在人群中的发病率为 1/40000。耳畸形是 BOS/BORS 的最明显的临床表现之一，包括外耳、中耳和内耳的畸形和听力损失，可为传导性、感觉神经性或混合性，从轻度到重度损失不等。颞骨影像学可协助临床医生诊断中耳和内耳畸形。包括直接测序结合下一代测序（NGS）、多重连接依赖性探针扩增（MLPA）或基于阵列的比较基因组杂交（aCGH）在内的多种方法可有效筛选和识别 BOS/BORS 的致病基因和/或变异类型。大约 40%的 BOS/BORS 患者携带 基因的异常，这是 BOS/BORS 最重要的原因。迄今为止，不同人群已报道了 基因的 240 种致病性变异，包括移码、无义、错义、异常剪接、缺失和复杂重排。人类内源性逆转录病毒序列（HERVs）可能在介导非等位基因同源重组引起的 染色体片段缺失突变中发挥重要作用。 编码一种与转录因子 合作的磷酸酶激活子，参与颅神经感觉发生和鳃弓衍生器官的发育，然后调节外耳、中耳和内耳向正常组织的形态和功能分化。此外， 基因和 基因的致病性突变也可导致 BOS/BORS。上述基因的变异可能通过破坏 SIX1-EYA1、SIX5-EYA1 或 SIX1-DNA 之间的结合而导致疾病。然而， 基因在 BORS 发病机制中的作用需要进一步验证。
