Sun Da-Peng, Dai Yun-Hai, Pan Xiao-Jing, Shan Tao, Wang Dian-Qiang, Chen Peng
State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, Shandong Province, China.
Qingdao University, Qingdao 266071, Shandong Province, China.
Int J Ophthalmol. 2017 Jun 18;10(6):847-853. doi: 10.18240/ijo.2017.06.04. eCollection 2017.
To describe a Chinese family affected by a severe form of Axenfeld-Rieger syndrome (ARS) and characterize the molecular defect in 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 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 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 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 have been found.
描述一个受严重形式的阿克森费尔德-里格尔综合征（ARS）影响的中国家庭，并确定该家庭中的分子缺陷。
对来自一个中国家庭的典型ARS患者进行调查。我们进行了全基因组连锁扫描和外显子组测序以鉴定致病突变。使用桑格测序法验证候选突变在整个家系中的共分离情况。进行实时聚合酶链反应（RT-PCR）和蛋白质印迹法以验证致病基因的表达。
全基因组连锁和外显子组测序分析显示[具体基因]为疾病候选基因。在该家庭中发现外显子5的3'ss第-11位的A>G替换（IVS5-11A>G）与疾病表型共分离。该家庭中ARS患者的信使核糖核酸和蛋白质水平比未受影响的家庭成员低约50%。
我们的研究结果表明[具体基因]的首个内含子突变与一个中国家庭中严重形式的ARS发病机制有关。这项研究强调了在未发现[具体基因]外显子突变的ARS病例中系统搜索内含子突变的重要性。
