一例眼-面-心-牙综合征患者的临床表型特征及分子遗传学研究

Clinical phenotype and molecular genetic study of a case with oculo-facio-cardio-dental syndrome

目的对一罕见的眼-面-心-牙（OFCD）综合征患者家系进行临床表型特征随访研究及致病基因突变筛查研究。方法实验研究。对患者进行详尽的临床多科室检查及表型资料收集。应用聚合酶链式反应（PCR）和Sanger测序法对OFCD患者及其父母进行候选基因BCOR的突变筛查，对携带碱基改变的序列进行单链PCR克隆产物的测序验证，并在60名无关正常对照人群中进行测序验证。结果表型研究结果提示患者存在眼部、面部、心脏、牙齿和肢体的先天发育异常，同时合并有脉络丛乳头状瘤表型，患者父母的临床表型未见异常，患者被确诊为OFCD综合征。候选基因突变筛查研究发现患者BCOR基因外显子4存在一个新的杂合缺失突变c．1296delT，该突变在患者父母及正常人群中没有检测到。结论本研究首次报道了一例OFCD综合征合并脉络丛乳头状瘤的表型，拓展了OFCD综合征的疾病表型谱。候选基因突变筛查发现了BCOR基因外显子4的一个新缺失突变c．1296delT，该突变导致0FcD综合征的发生。

Objective To analyze the clinical phenotypes in a family with rare oculo-facio- cardio-dental （OFCD） syndrome and to identify the pathogenic mutation. Methods This was an experimental study. All participants underwent detailed clinical examinations and phenotype data collection. Mutation analyses of the candidate gene BCOR were performed for the patient and her parents to detect the potential mutation by using polymerase chain reaction （PCR） and Sanger sequencing. The single stranded PCR cloning products that carry the nucleotide alterations were sequenced. PCR and sequencing verification were also carried out in 60 unrelated normal control individuals. Results Phenotypic study indicated that this patient with eye, craniofacial, heart, dental, and limb anomalies and papilloma of the ehoroid plexus, was diagnosed to have OFCD syndrome. No abnormal results were found with her parents. A novel deletion mutation c.1296delT in exon 4 of the BCOR gene was identified in this patient; this change was not found in her parents or in 60 normal unrelated individuals. Conclusion We report on a rare case of OCFD. Papilloma of the choroid plexus was found in an OFCD patient for the first time, expanding the clinical phenotype spectrum of OFCD. Meanwhile, it is a novel deletion mutation c.1296delT of the BCOR gene that causes OFCD.