Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology & Visual Sciences, Beijing, 100005, China.
Beijing Tongren Eye Center, Beijing Tongren Hospital of Capital Medical University, Beijing Key Laboratory of Ophthalmology and Visual Sciences, Beijing, 100005, China.
Sci China Life Sci. 2019 Jan;62(1):119-125. doi: 10.1007/s11427-018-9374-2. Epub 2018 Sep 21.
The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental (OFCD) syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296delT in exon 4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome.
本研究旨在分析 1 例眼面心牙(Oculo-facio-cardio-dental,OFCD)综合征患儿的临床表型,并鉴定导致其疾病的潜在致病性突变。该患儿接受了详细的临床检查,并在 9 年的随访期间收集了表型数据。采用聚合酶链反应(PCR)和 Sanger 测序对候选基因 BCOR 进行突变分析。同时,对 60 名无亲缘关系的正常个体的 BCOR 进行测序作为对照组。临床表型和随访研究结果表明,该患儿存在多种系统异常,包括眼部、面部、心脏、牙齿和四肢畸形。此外,还发现脉络丛乳头状瘤,这是 OFCD 患者中首次报道该表型。在该患儿中发现了 BCOR 基因外显子 4 中的 c.1296delT 新型缺失突变,其父母及 60 名无亲缘关系的正常个体中均未发现该突变。该缺失突变导致移码,可能会导致提前终止密码子的产生,从而导致截短蛋白的产生。本患儿符合 OFCD 综合征的诊断标准,我们首次报道了 OFCD 患儿发生脉络丛乳头状瘤,扩展了该疾病的已知表型谱。同时,我们鉴定了一种可能导致 OFCD 综合征的新型缺失突变。