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

• DOI: 10.18240/ijo.2017.06.04
• Publication Date: 2017-06-15T07:41:39Z
• Authors: Xiao-Jing Pan; Dian-Qiang Wang; Da-Peng Sun; Shan Tao; Chen Peng; Yunhai Dai
• Keywords: 0301 basic medicine; Ophthalmology; 03 medical and health sciences; 853; linkage analysis; PITX2; RE1-994; intronic mutation; exome sequencing; Axenfeld-Rieger syndrome; 3. Good health

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.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.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.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.