Genetic screening of the congenital aniridia and genotype-phenotype analysis / 中华实验眼科杂志

Objective@#To explore the genotype-phenotype correlation among 3 pedigrees affected with congenital aniridia.@*Methods@#Clinical data and genomic DNA were collected and genetic variations were screened by whole-exome sequencing, with an emphasis on PAX6-related genes.Suspected variations were verified by Sanger sequencing and quantitative polymerase chain reaction (PCR). Written informed consent was obtained from the parents of each propositus prior to entering study cohort.This study protocol was approved by Ethic Committee of Henan Eye Hospital (No.HNEECKY-2017(6)).@*Results@#Genetic analysis identified that a nonsense c. 949 C>T variation and an c. 141+ 1 G>T splicing variation of the PAX6 gene in two of the probands, while the remainder has carried a duplication in 11 p13 (chr11: 31531331-31827959) encompassing the PAX6 and ELP4 genes.Phenotype analysis showed that the probands carrying the nonsense and splicing variations had classical features including complete aniridia, macular hypoplasia, microcornea and nystagmus; the proband carrying the 11p13 duplication had microphthalmos, microcornea, macular dysplasia, iris dysgenesis, and nystagmus.@*Conclusions@#The 11p13 duplication involving the PAX6 gene may have caused over-expression of PAX6 gene, resulting in severe eye abnormalities including microphthalmos and microcornea, macular dysplasia and nystagmus.The relatively mild iris dysgenesis has distinguishing it from classical aniridia due to PAX6 haploinsufficiency.

Mutation analysis of a family affected with congenital aniridia and congenital cataract / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To identify the potential mutation in a Chinese family affected with congenital aniridia and cataract, which can expands the mutation spectrum of antosomal dominant congenital aniridia.<p>METHODS: A Chinese family with congenital aniridia and cataract and 100 unrelated controls were recruited, peripheral venous blood was collected for genomic DNA extraction. Candidate genes sequencing was performed by direct DNA sequencing to screen out the <i>PAX6 </i>mutation.<p>RESULTS: All affected individuals in the family showed aniridia and cataract. A novel non-sense mutation c.991 C>T in exon 11 of <i>PAX6</i> was exclusively observed in all affected individuals but not in any of the unaffected family members or unrelated controls, which results in the truncation of encoding protein(R331X). <p>CONCLUSION: We identified a novel mutation in the <i>PAX6</i> R331X, which may be responsible for the pathogenesis of congenital aniridia and cataract.

Mutation analysis of Pax6 in Chinese patients with congenital aniridia / 中华实验眼科杂志

Background Congenital aniridia is a rare congenital autosomal dominant disease,which is shown as aniridia of double eyes,and the paired box gene 6 (Pax6) gene mutation is now known to be associated with congenital aniridia.Objective This study was to screen the Pax6 gene mutation in patients with congenital aniridia.Methods Eleven patients with congenital aniridia were enrolled in Tianjin Eye Hospital from August 2012 to October 2015,including 6 patients from 3 congenital aniridia family and 5 sporadic patients.All patients received routine ophthalmic examination.Peripheral venous blood of 3 ml was collected from the patients for DNA extraction according to the standard process of DNA isolation instructions,and all the exons of Pax6 gene,Elp4 gene,exon 5 ' and 3',intron splice sequence and SIMO sequence were amplified by PCR.Pax6 genes of the patients were sequenced using Sanger direct sequencing and multiplex ligation dependent probe amplification (MLPA) and compared with those of 500 ocular trauma patients.This study complied with Helsinki declaration,and written informed consent was obtained from each patient prior to any medical examination.Results Iris absence was found in all the patients,and the visions acuity was hand motion to 0.2.Lens dislocation was seen in 1 patient.Direct sequencing results found that three patients in AN-O1 family were c.688g＞t (p.E230X) mutation of Pax6 gene,and 3 of 5 sporadic patients carried c.468g＞a (p.W156X),c.613c＞t (p.Q205X) and c.141 +2t＞c mutant of Pax6 gene,and the c.688g＞t (pE230X) mutation was a novel-discovered mutation.No any mutation in Pax6,Elp4 gene and SIMO fragment was detected in 1 patient from AN-02 family,2 patients from AN-03 family and 2 sporadic patients by both direct sequencing and MLPA validation.No above-mentioned mutation was found in 500 normal individuals.Conclusions The mutation of Pax6 gene is a pathogenic mutation in congenital aniridia patients,and c.688g＞t (p.E230X) is a novel Pax6 mutant,which expanded the mutation spectrum of Pax6 gene.

A nonsense PAX6 mutation in a family with congenital aniridia / 소아과

Congenital aniridia is a rare ocular malformation that presents with severe hypoplasia of the iris and various ocular manifestations. Most cases of congenital aniridia are known to be related to mutations in the paired box gene-6 (PAX6), which is an essential gene in eye development. Herein, we report a familial case of autosomal dominant congenital aniridia with four affected members in 3 consecutive generations and describe the detailed ophthalmologic findings for one of these members. As expected, mutational analysis revealed a nonsense mutation (p.Ser122*) in the PAX6 gene. Thus, our findings reiterate the importance of PAX6 mutations in congenital aniridia.

Recurrent progressive anterior segment fibrosis syndrome following a descemet-stripping endothelial keratoplasty in an infant with congenital aniridia.

Progressive anterior segment fibrosis syndrome (ASFS), after intraocular surgery in older children (≥9 years) and adults with congenital aniridia, is described in the literature. In this report, we describe an unique case of ASFS in an infant with congenital aniridia following a combined trabeculotomy‑ectomy and its recurrence after a descemet stripping endothelial keratoplasty. The ophthalmologists should be well aware of this entity and warn the parents about its possibilities. Use of immunomodulators or prolonged anti‑inflammatory therapy may be considered to prevent its occurrence.

Phenotype of congenital cataract accompanied with iris dysplasia / 中华实验眼科杂志

Background Certain relationship has been found between phenotype and genes mutation of congenital cataract.It is clear that different genetic mutations can cause the same complication in congenital cataract,meanwhile,different complications may be caused by the same gene mutation.However,their mechanism is still remained unclear.Objective This study was to observe the phenotype of congenital cataract accompanied with iris dysplasia.Methods Fifteen patients with congenital cataract accompanied with iris dysplasia were included in this study.The slit lamp,gonioscope and ophthalmoscope were used for the examination of the anterior ocular segment,the anterior chamber angle and fundus on all the patients.This study was approved by the Ethic Committee of Second People' s Hospital of Yunnan Province.Written informed consent was obtained from each patient or the custodian prior to any medical procedure.Results All the patients showed binocular involvement.Congenital nuclear cataract with whole coloboma of iris was seen in 7 cases,and 2 cases showed an entire cataract associated with incomplete coloboma of iris.Entire cataract with aniridia was diagnosed in 5 patients,and suture cataract complicated with aniridia was in 1 patient.Conclusions Some regular patterns can be implied between the morphological type of cataract and iris dysplasia,which may be helpful for further study of these diseases.

Clinical Features of Korean Patients with Congenital Aniridia

PURPOSE: To investigate the clinical features of Korean patients with congenital aniridia. METHODS: This retrospective study focused on 60 eyes from 31 patients who were diagnosed with congenital aniridia at Kangnam St. Mary's Hospital from 1996 to 2007. Patient age, gender, visual acuity (VA), family history, and previous ocular history were recorded. The presence of keratopathy, glaucoma, cataract, foveal hypoplasia, and other ocular or systemic anomalies were evaluated for each patient. RESULTS: The proportion of sporadic cases was 29.0%. Cataract (82.5%), glaucoma (51.6%), keratopathy (71.6%), and foveal hypoplasia (81.8%) commonly accompanied aniridia. Thirty-four (60.7%) eyes had VAs less than 20/200 and 20 eyes (35.7%) had VAs between 20/200 and 20/60. In patients without a past history of ocular surgery, the mean central corneal thickness was 643.05 +/- 37.67 microm and the mean endothelial cell count was 3,349.44 +/- 408.17 cells/mm2. Ocular surface surgeries were performed in 6 eyes. The clarity of the transplanted corneal graft vanished in 5 eyes with the progression of peripheral neovascularization and subepithelial fibrosis. The mean age of cataract surgery in 8 eyes was 29.8 +/- 5.9 years. Postoperative worsening of corneal clouding and glaucomatous damage were observed in 4 eyes. Two infants had bilateral congenital glaucoma. Two children with sporadic aniridia were identified to have Wilm's tumors. CONCLUSIONS: Congenital aniridia is a progressive congenital disorder that is commonly accompanied by complications that can lead to impaired vision. Regular, careful examinations for these accompanying complications should be performed in all patients with congenital aniridia.

A Case of Anterior Fibrovascular Membrane After Intraocular Lens Implantation in Congenital Aniridia

PURPOSE: To report a case of an anterior fibrovascular membrane following cataract extraction and intraocular lens implantation in a patient with congenital aniridia. CASE SUMMARY: A 13-year-old girl presented with congenital aniridia and cataracts in both eyes. She underwent cataract extraction by phacoemulcification with intraocular lens implantation. Six months after cataract surgery, a progressive anterior chamber fibrovascular membrane was noted in both intraocular lens and rudimentary iris. Surgical excision of the fibrovascular membrane was performed, but there was recurrence after five weeks in both eyes. Subsequent surgical intervention on both eyes involved intraocular lens explantation combined with membranectomy to prevent recurrence and phthisis. Surgical findings indicated that the fibrovascular membrane involved the retrolenticular space, and histopathological evidence indicated that the extensive fibrotic tissue originated from the root of the rudimentary iris. CONCLUSIONS: Patients with congenital aniridia should be monitored carefully for the development of intraocular fibrosis after intraocular lens implantation. If a fibrovascular membrane is noted, early surgical intervention is recommended, and the explantation of the intraocular lens should be considered during surgical intervention to prevent recurrence and complications.

Clinical Results of Black-Diaphragm Intraocular Lens Implantation

PURPOSE: We studied the clinical products of sulcus fixation of Black-diaphragm intraocular lens and transscleral fixation of Black-diaphragm intraocular lens in congenital and acquired aniridia patients. METHODS: We retrospectively analyzed the records of 12 aniridic eyes in 20 patients who underwent Black-diaphragm intraocular lens implantation from December 2001 to December 2003 at our hospital. We divided the aniridia eyes into sulcus fixation (group 1, 3 eyes of 3 patients) and transscleral fixation (group 2, 8 eyes of 8 patients) groups, and congenital aniridia (group A, 3 eyes of 3 patients) and acquired anirida (group B, 9 eyes of 9 patients) groups. We compared results between groups 1 and 2, and between groups A and B. RESULTS: The differences (in diopter) between preoperatively expected refractive error and postoperative refractive error were -1.27 +/- 1.06 in group 1 and -1.06 +/- 1.06 in group 2, and this difference between groups 1 and 2 was not significant. Postoperative visual acuity results in group A (0.18 +/- 0.03) were significantly better than those in group B (0.61 +/- 0.29). CONCLUSIONS: In Black-diaphragm intraocular lens implantation of aniridia patients, the differences between preoperatively expected refractive error and postoperative refractive error were not different between sulcus fixation and transscleral fixation. Better postoperative visual acuity results are anticipated in acquired aniridia patients than in congenital aniridia patients.

Implantation of Black Diaphragm Intraocular Lens in Cataract Surgery with Congenital Aniridia

Cogenita aniridia is a relatively rare congenital anomay and its incidence is about 1:100,000. It occurs along with cataract(85%) and nystagmus(92%). Black diaphragm intraocular lenses(IOLs) were inserted in five eyes of congenital aniridia with cataract. Nystagmus was seen in all eyes, while lens subluxation was observed in two eyes. The IOLs were inserted into the ciliary sulci in two eyes with lens subluxation, and the capsular bag in three eyes. In all testing eyes, we tested preoperative and postoperative visual acuity, intraocular pressure, and preformed routine ocular examinations. We also examined multivision contrast test(MCT) in two eyes. Postoperative visual acuity improved in all cases, but the intraocular pressure increased only in one eye. The nystagmus slightly decreased in all cases. The result of postoperative MCT was the same as that of preoperative. But in the other cases, the glare decreaed. By insertion of the black diaphragm IOL, we achieved the improvement of visual acuity, the decrease of glare and nystagmus, and cosmetic effect.