A Chinese family with Axenfeld-Rieger syndrome:report of the clinical and genetic findings  

作　　者：Da-Peng Sun Yun-Hai Dai Xiao-Jing Pan Tao Shan Dian-Qiang Wang Peng Chen Da-Peng Sun;Yun-Hai Dai;Xiao-Jing Pan;Tao Shan;Dian-Qiang Wang;Peng Chen(State Key Laboratory Cultivation Base,Shandong Provincial Key Laboratory of Ophthalmology,Shandong Eye Institute,Shandong Academy of Medical Sciences;Qingdao University)

机构地区：[1]Qingdao University, Qingdao 266071, Shandong Province, China [2]State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, China

出　　处：《International Journal of Ophthalmology(English edition)》2017年第6期847-853,共7页国际眼科杂志（英文版）

基　　金：Supported by China Postdoctoral Science Foundation Funded Project(No.2017M612211);the National Natural Science Foundation of China(No.81300742;No.81600721);the Shandong Province Medical and Health Technology Development Project(No.2016WS0265);the Science and Technology Plan of Qingdao(No.15-9-1-35-jch)

摘　　要：AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chinese family were investigated. We performed genome- wide linkage scan and exome sequencing to identify the pathogenic mutations, Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing, Real-time polymerase chain reaction （RT- PCR） and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS： Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A〉G substitution at position -11 of 3＇ss of exon 5 （IVS5- 11A〉G） that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family, CONCLUSION： Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.AIM： To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome （ARS） and characterize the molecular defect in PITX2 in the family. METHODS： Patients presented with typical ARS from a Chinese family were investigated. We performed genome- wide linkage scan and exome sequencing to identify the pathogenic mutations, Candidate mutations were verified for co-segregation in the whole pedigree using Sanger sequencing, Real-time polymerase chain reaction （RT- PCR） and Western blotting were performed to verify the expression of the pathogenic gene. RESULTS： Genome-wide linkage and exome sequencing analyses showed PITX2 as the disease candidate gene. A〉G substitution at position -11 of 3＇ss of exon 5 （IVS5- 11A〉G） that co-segregated with the disease phenotype was discovered in the family. The PITX2 messenger ribonucleic acid and protein levels were about 50% lower in patients with ARS than in unaffected family members in the family, CONCLUSION： Our findings implicate the first intronic mutation of the PITX2 gene in the pathogenesis of a severe form of ARS in a Chinese family. This study highlights the importance of a systematic search for intronic mutation in ARS cases for which no mutations in the exons of PITX2 have been found.

关 键 词：Axenfeld-Rieger syndrome exome sequencing linkage analysis PITX2 intronic mutation 

分 类 号：R771[医药卫生—眼科]