Division of Human Genetics, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Faculté de Médecine et d'Odondostomatologie, USTTB, Bamako, Mali.
Mol Genet Genomic Med. 2022 Jul;10(7):e1995. doi: 10.1002/mgg3.1995. Epub 2022 Jun 14.
Branchio-otic syndrome (BO) is one of the most common types of syndromic hearing impairment (HI) with an incidence of 1/40,000 globally. It is an autosomal dominant disorder typically characterized by the coexistence of branchial cysts or fistulae, malformations of the external, middle, and inner ears with preauricular pits or tags and a variable degree of HI. Most cases of BO have been reported in populations of European ancestry. To date, only few cases have been reported in people from African descent.
After a careful clinical examination, a pure tone audiometry was performed. DNA was extracted from peripheral blood and whole exome, and Sanger sequencing were performed for genetic analysis.
Eight individuals from a large non-consanguineous Malian family, with autosomal dominant inheritance were enrolled. The ages at diagnosis ranged from 8 to 54 years. A high phenotypic variability was noted among the affected individuals. Four patients presented with a post-lingual and mixed type of HI, one individual had conductive HI while three had normal hearing but presented other BO features namely branchial fistulae and preauricular sinus. Serum creatinine level and renal ultrasonography were normal in three affected individuals who performed them. Genetic testing identified a monoallelic pathogenic variant in EYA1 (c.1286A > G; p.Asp429Gly) segregating with BO syndrome in the family.
This is the first genetically confirmed case of BO syndrome caused by EYA1 variant in the sub-Saharan African population, expanding the genetic spectrum of the condition.
耳颌畸形综合征（BO）是最常见的综合征性听力损失（HI）类型之一，全球发病率为 1/40000。它是一种常染色体显性遗传疾病，通常表现为鳃裂囊肿或瘘管、外耳、中耳和内耳畸形，伴有耳前凹或耳前赘生物和不同程度的 HI。大多数 BO 病例发生在欧洲血统的人群中。迄今为止，只有少数来自非洲裔人群的病例报告。
经过仔细的临床检查，进行了纯音听阈测试。从外周血中提取 DNA，并进行全外显子测序和 Sanger 测序进行遗传分析。
从一个大型非近亲的马里家族中纳入了 8 名具有常染色体显性遗传的个体。诊断时的年龄范围为 8 至 54 岁。受影响个体的表型变异性很大。4 名患者表现为后天性和混合性 HI，1 名患者表现为传导性 HI，而 3 名患者听力正常，但表现出其他 BO 特征，即鳃裂瘘管和耳前窦。进行这些检查的 3 名受影响个体的血清肌酐水平和肾脏超声检查均正常。基因检测确定了 EYA1 中的单等位基因致病性变异（c.1286A>G；p.Asp429Gly），该变异与家族中的 BO 综合征共分离。
这是首例在撒哈拉以南非洲人群中由 EYA1 变异引起的 BO 综合征的基因确诊病例，扩展了该疾病的遗传谱。
