Estefanía E, Ramírez-Camacho R, Gomar M, Trinidad A, Arellano B, García-Berrocal J R, Verdaguer J M, Vilches C
Servicio de Inmunología, ENT Department, Hospital Universitario Puerta de Hierro, Universidad Autonoma de Madrid, Spain.
Ann Hum Genet. 2006 Jan;70(Pt 1):140-4. doi: 10.1111/j.1529-8817.2005.00204.x.
Mutations of the EYA1 gene (8q13.3) are the most common known cause of the branchio-oto-renal dysplasia (BOR), an autosomal dominant disease that includes developmental defects of branchial arch structures, middle and/or inner ear and kidney. The distinction between BOR and other dysplasias, such as oto-facio-cervical syndrome (OFC), is challenged by frequent association of the former to other diverse malformations, and by variable expressivity even within the same family. OFC is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR. Recent characterization of one OFC patient shed some light on the controversy over whether OFC and BOR are the same disease, and led to the hypothesis that OFC is caused by contiguous deletions of EYA1 and adjacent genes. By contrast, we show here that an OFC patient bears a single-nucleotide substitution in a splice site of EYA1. Our results indicate that not only major rearrangements, but also point mutations altering the EYA1 reading frame, can be found in patients with OFC syndrome.
EYA1基因（8q13.3）突变是鳃-耳-肾发育异常（BOR）最常见的已知病因，BOR是一种常染色体显性疾病，包括鳃弓结构、中耳和/或内耳以及肾脏的发育缺陷。BOR与其他发育异常（如耳-面-颈综合征，OFC）之间的区分受到挑战，原因在于前者常与其他各种畸形相关，且即使在同一家族中其表现度也存在差异。OFC的特征除了有BOR中所见的畸形外，还包括面部和肩胛带的营养性改变。最近对一名OFC患者的特征分析为OFC和BOR是否为同一种疾病的争议提供了一些线索，并引发了一种假说，即OFC是由EYA1及相邻基因的连续性缺失所致。相比之下，我们在此表明一名OFC患者在EYA1的一个剪接位点存在单核苷酸替换。我们的结果表明，在OFC综合征患者中不仅能发现重大重排，还能发现改变EYA1读码框的点突变。
