摘要目的:研究中国汉族Axenfeld-Rieger综合征(ARS)一家系临床表现及其基因特征。方法:采用家系调查研究方法，纳入2024年1月于河南省立眼科医院就诊的中国汉族ARS一家系3人，其中患者1例。收集先证者及其父母的临床资料，进行全面的眼科检查及全身一般检查。采集家系成员的外周血并提取DNA，对先证者进行全外显子组测序，采用实时荧光定量PCR验证家系成员 ZBED1P1、 ENPEP、 PITX2、 FAM241A基因的拷贝数。以"Axenfeld-Rieger综合征"、"Axenfeld-Rieger syndrome"和" PITX2"为主题词，检索OMIM、ClinVar、PubMed、中国知网、万方数据、维普网、DECIPHER、Google Scholar数据库，总结中国人群 PITX2微缺失相关ARS文献中不同患者的临床表现及微缺失类型，分析基因型和临床表型的关系。 结果:先证者女，25岁，临床表现为双眼小角膜，多瞳孔，瞳孔变形、移位，面中部扁平，上颌骨发育不良，牙齿缺失，脐部突出等；其父母表型正常。DNA测序显示先证者携带1个4q25上1.06 Mb微缺失。实时荧光定量PCR验证该4q25微缺失包含 PITX2和 ENPEP基因，且先证者父母均无该缺失；ClinGen CNV致病性评级显示该包含 PITX2基因缺失为新发致病性拷贝数变异(CNV)。共检索出5篇4q25微缺失相关中国ARS文献，对所述的13例患者临床特征进行总结发现，有角膜疾病占100%、表现出脐疝和牙齿异常占92%、眼压异常占62%、虹膜萎缩占46%、角膜后胚胎环占31%。 结论:在中国汉族ARS一家系中，先证者具有含 PITX2基因在内的新发致病性4q25微缺失变异，表现出小角膜、先天性虹膜发育不良、多瞳症、牙齿缺失、脐部皮肤突出等典型表型。

abstractsObjective:To investigate the clinical manifestations and genetic characteristics of a Chinese Han family with Axenfeld-Rieger syndrome (ARS).Methods:A pedigree study was conducted.Three people from a Chinese Han family with ARS who visited Henan Eye Hospital in January 2024 were included, including 1 patient.Clinical data of the proband and her parents were collected.Comprehensive ophthalmic examination and general physical examination were performed on the proband and her parents.Peripheral blood samples were obtained from family members for DNA extraction.Whole exome sequencing was performed on the proband, and the copy number of the ZBED1P1, ENPEP, PITX2, and FAM241A genes in family members were validated using the real-time fluorescent quantitative PCR.Axenfeld-Rieger syndrome, Axenfeld-Rieger Syndrome, and PITX2 were used as keywords to search across databases such as OMIM, ClinVar, PubMed, CNKI, Wanfang, VIP, DECIPHER, and Google Scholar.The clinical manifestations and microdeletion types of different patients in ARS literature related to PITX2 microdeletions in China population were summarized, and the relationship between genotype and clinical phenotype was analyzed.The study followed the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEEC-2024[34]).All subjects understood the purpose of the study and voluntarily signed the informed consent form. Results:The proband was a 25-year-old female, exhibiting diminutive cornea in both eyes, polycoria, deformation and displacement of pupils, a flat mid-face, maxillary dysplasia, tooth loss, and a protruding umbilicus, among other symptoms.Parents of the proband were phenotypically normal.DNA sequencing identified a 1.06 MB microdeletion on chromosome 4q25 in the proband.Real-time quantitative PCR confirmed that this microdeletion encompassed the PITX2 and ENPEP genes, and it was absent in the proband's parents.The ClinGen CNV pathogenicity scoring indicated that the deletion involving the PITX2 gene represented a novel pathogenic copy number variation (CNV).Five studies related to 4q25 microdeletion in Chinese families with Axenfeld-Rieger syndrome was screened, including 13 patients.Clinical manefestations of the 13 patients included corneal disorders (accounting for 100%), umbilical hernia and dental anomalies (accounting for 92%), irregular intraocular pressure (accounting for 62%), iris atrophy (accounting for 46%), and posterior corneal embryotoxon (accounting for 31%). Conclusions:For this Chinese family diagnosed with ARS, a novel pathogenic 4q25 microdeletion variant encompassing the PITX2 gene was found in the proband, which is associated with characteristic phenotypes including microcornea, congenital iris dysplasia, polycoria, tooth loss, and a protruding umbilicus.