Mirrahimi Mehraban, Sabbaghi Hamideh, Ahmadieh Hamid, Jahanmard Mehdi, Hassanpour Kiana, Suri Fatemeh
a Ocular Tissue Engineering Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.
b Ophthalmic Epidemiology Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.
Ophthalmic Genet. 2019 Apr;40(2):146-149. doi: 10.1080/13816810.2019.1597374. Epub 2019 Apr 15.
Aniridia is a rare developmental eye disorder characterized by complete or partial iris hypoplasia often accompanied with other ocular changes that affect the cornea, anterior chamber, lens, retina, and optic nerve. Most cases of aniridia are inherited with an autosomal dominant mode of inheritance caused by PAX6 mutations or deletions. To reveal the underlying genetic defect in a four-generation Iranian family with aniridia, we carried out a genetic screening of PAX6.
Complete ophthalmic examinations were performed for available affected family members. All PAX6 exons and their flanking regions were sequenced for affected individuals. Candidate variation was screened for segregation in the pedigree by Sanger sequencing. Bioinformatics prediction was done to evaluate the deleterious effects of the mutation on protein product. Real-time PCR was used to investigate the impact of the variant on PAX6 mRNA expression.
All patients were diagnosed with isolated aniridia associated with variable phenotypic features including retinal detachment. A novel heterozygous deletion c.320_348delTGTCCGAGGGGGTCTGTACCAACGATAAC (p.Leu107HisfsX16) on PAX6 gene was detected. Decreased mRNA level of PAX6 in the affected individuals indicated that the mutation caused nonsense-mediated mRNA decay (NMD).
To the best of our knowledge, it is the first report on the genetics of aniridia in Iran. Segregation analysis, bioinformatics prediction and confirmation of NMD, all support the proposition that the novel observed PAX6 mutation is the cause of aniridia in the pedigree. Retinal detachment in some of the affected members, which is a rare reported phenotypic feature of aniridia patients, may be associated with this mutation.
无虹膜症是一种罕见的发育性眼病，其特征为虹膜完全或部分发育不全，常伴有影响角膜、前房、晶状体、视网膜和视神经的其他眼部变化。大多数无虹膜症病例以常染色体显性遗传模式遗传，由PAX6基因突变或缺失引起。为揭示一个患有无虹膜症的四代伊朗家族潜在的基因缺陷，我们对PAX6进行了基因筛查。
对所有可及的患病家族成员进行全面眼科检查。对患病个体的所有PAX6外显子及其侧翼区域进行测序。通过Sanger测序筛选候选变异在系谱中的分离情况。进行生物信息学预测以评估该突变对蛋白质产物的有害影响。采用实时PCR研究该变异对PAX6 mRNA表达的影响。
所有患者均被诊断为孤立性无虹膜症，伴有包括视网膜脱离在内的多种可变表型特征。在PAX6基因上检测到一个新的杂合缺失c.320_348delTGTCCGAGGGGGTCTGTACCAACGATAAC（p.Leu107HisfsX16）。患病个体中PAX6的mRNA水平降低表明该突变导致了无义介导的mRNA降解（NMD）。
据我们所知，这是伊朗关于无虹膜症遗传学的首例报道。分离分析、生物信息学预测以及NMD的证实，均支持所观察到的新PAX6突变是该系谱中无虹膜症病因这一观点。部分患病成员出现的视网膜脱离，这是无虹膜症患者罕见的报道表型特征，可能与该突变有关。
