A Chinese family with Axenfeld-Rieger syndrome: report of the clinical and genetic findings
A Chinese family with Axenfeld-Rieger syndrome: report of the clinical and genetic findings
复制标题
一个中国 Axenfeld-Rieger 综合征家系：临床和遗传学发现报告
DOI：
10.18240/ijo.2017.06.04
复制
发表时间：
2017-06-18
影响因子：
1.4
通讯作者：
Chen, Peng
中科院分区：
文献类型：
--
作者：
Sun, Da-Peng;Dai, Yun-Hai;Chen, Peng
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 (RTPCR) 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.
