| Purpose To analyze the clinical features of aniridia and other developmental eye diseases. And identify the causal genes and mutations, aiming to study the correlation of genotypes and phenotypes.Methods 8 aniridia pedigrees and 7 pedigrees with other developmental anomalies (in-cluding Anterior Segment Dysgenesis, Microphthalmia and Microcornea) diagnosed in the clinic during 2010 to 2016 were collected retrospectively. Medical history and family his-tory were recorded, the patients were performed with ophthalmic examinations and optical coherence tomography (OCT). Venous blood (5 ml) from the patients and relatives were collected and extracted into genomic DNA. For the anirdia patients, PAX6 gene was am-plified and Sanger sequencing was performed. Next-generation sequencing was performed on the patients with other developmental eye diseases. For the samples we couldn’t locate the causal mutation via Sanger sequencing, we performed MLPA (PAX6) test to detect large deletions/duplications. Then segregation was performed among the pedigrees to further confirm the causal mutation.Results 23 patients (including the probands and affected relatives) from 15 pedigrees were collected, among them were 11 patients with anirdia in 8 pedigrees and 12 patients with other developmental eye diseases in 7 pedigrees.1. Clinical manifestations:(1) 7 aniridia pedigrees inherited in the autosomal dominant (AD) fashion and 1 case was sporadic. The 11 aniridia patients were all bilateral affected, among the 22 affected eyes, the visual acuity (VA) ranged from 0.01 to 0.4 with the median VA 0.1. All the patients had nystagmus,9 (81.8%) patients’iris were complete aplasia,2 (18.2%) patients’were partial aplasia.2 (18.2%) patients were associated with bilateral ptosis.4 patients had OCT scan and all of them had fovea hypogenesis. (2) The phenotypes of the 7 pedigrees include cornea opacity, iris hypoplasia associated glaucoma (3 patients in 1 pedigree); nystagmus, presenile cataract and foveal hypogenesis (4 patients in 1 pedi-gree); 2 cases with microphthalmia; 2 cases had congenital cataract associated with micro-cornea; 1 case had congenital cataract associated choroidal coloboma. Among them,5 ped-igrees inherited in AD fashion, and 2 cases were sporatic.10 patients were bilateral affected and 2 were unilateral. Among the 22 affected eyes, the VA ranged from NLP to 0.3, with the median VAFC.2. Molecular genetics results:(1) All the 8 aniridia pedigrees were found PAX6 changed including 6 heterozygous mutations and 2 large deletions in chromosome 11.6 mutations included 1 missense mutation (16.7%),2 nonsense mutations (33.3%),1 frameshift muta-tion (33.3%) and 1 splicing mutation. (2) Among the 7 other pedigrees,3 were found PAX6 changed including 2 missense mutations and 1 large fragment duplication.2 pedigrees were found CRYGC mutation, including 1 missense and 1 nonsense.1 patient had a mis-sense mutation in CRYBB1.1 patient was found a missense mutation in GDF6 gene. In this study,6 novel mutations and 3 novel large fragment change were located in PAX6. And 1 novel mutation in CRYBB1,2 novel mutations in CRYGC were found respectively.Conclusion Aniridia and other developmental eye disease can cause very poor vision, and different eye structure anomalies can occur combinedly. In this study, PAX6 is the causal gene in 11 pedigrees, indicates that PAX6 has an important role in developmental eye dis-eases. There is no clear correlation between the phenotype and genotype in this study, in-dicates that there are some non-genetic factors involved in ocular development. |
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