BACKGROUND: The aim of this study is to identify the genetic defect in a Chinese family with congenital aniridia combined with cataract and nystagmus.
METHODS: Complete ophthalmic examinations, including slit-lamp biomicroscopy, dilated indirect ophthalmoscopy, anterior segment photography, and anterior segment optical coherence tomography (OCT) were performed. Blood samples were collected from all family members and genomic DNA was extracted. Genome sequencing was performed in all family members and Sanger sequencing was used to verify variant breakpoints.
RESULTS: All the thirteen members in this Chinese family, including seven patients and six normal people, were recruited in this study. The ophthalmic examination of affected patients in this family was consistent with congenital aniridia combined with cataract and nystagmus. A novel heterozygous deletion (NC_000011.10:g.31802307_31806556del) containing the 5\' region of PAX6 gene was detected that segregated with the disease.
CONCLUSIONS: We detected a novel deletion in PAX6 responsible for congenital aniridia in the affected individuals of this Chinese family. The novel 4.25 kb deletion in PAX6 gene of our study would further broaden the genetic defects of PAX6 associated with congenital aniridia.

PAX6 is a transcription factor involved in embryonic development of many organs, including the eyes and the pancreas. Mutations of PAX6 gene is the main cause of a rare disease, congenital aniridia (CA). This case-control study aims to investigate the effects of PAX6 mutations on glucose metabolism and insulin secretion in families with CA.
In all, 21 families with CA were screened by Sanger sequencing. Patients with PAX6 mutations and CA (cases) and age-matched healthy family members (controls) were enrolled. Oral glucose tolerance test (OGTT) was performed to detect diabetes or impaired glucose tolerance (IGT). Insulin and proinsulin secretion were evaluated.
Among 21 CA families, heterozygous PAX6 mutations were detected in five families. Among cases (n = 10) from the five families, two were diagnosed with newly identified diabetes and another two were diagnosed with IGT. Among controls (n = 12), two had IGT. The levels of haemoglobin A1c were 36 ± 4 mmol/mol (5.57 ± 0.46%) and 32 ± 5 mmol/L (5.21 ± 0.54%) in the cases and the controls, respectively (p = 0.049). More importantly, levels of proinsulin in the cases were significantly higher than that of the controls, despite similar levels of total insulin. The areas under the curve of proinsulin in the cases (6425 ± 4390) were significantly higher than that of the controls (3709 ± 1769) (p = 0.032).
PAX6 may participate in the production of proinsulin to insulin and heterozygous PAX6 mutations may be associated with glucose metabolism in CA patients.

Purpose: To evaluate the choroidal thickness (CT) in children with congenital aniridia in comparison with age-matched controls. Methods: This was a cross-sectional, observational study that included 64 eyes of 32 children with congenital aniridia (aged 5-12 years) and 80 eyes of 40 healthy subjects who were age-matched. In all subjects, subfoveal choroidal thickness (SFCT) was assessed at 750-μm intervals from the fovea to 1.5 mm in the temporal and nasal directions with spectral-domain optical coherence tomography (SD-OCT). Results: The mean SFCT was 207.67 ± 30.99 µm in the aniridic eyes. This SFCT was significantly thinner than that in control eyes (288.55 ± 30.06 µm) (P < .001). The SFCTs at 1.5 mm and 0.75 mm intervals in the temporal and nasal directions from the fovea were also significantly thinner in eyes with aniridia than control eyes (P < .001).There was a significant negative correlation between the SFCT and axial length in eyes with aniridia (B = -10.60, 95%CI = -19.31~-1.89, P = .017). Conclusions: The subfoveal and parafoveal CTs were significantly thinner in eyes with congenital aniridia than in control eyes. These choroidal changes could open up a new way for the research related to the pathophysiology of congenital aniridia.

Congenital aniridia is a severe ocular abnormality characterized by incomplete formation of the iris and many other ocular complications. Most cases are caused by the paired box 6 (PAX6) gene mutations generating premature termination codons (PTCs).
Ophthalmic examination was performed on a Chinese pedigree with congenital aniridia. The mutation was identified by targeted next-generation sequencing. Nonsense suppression therapy was applied on patient-derived lymphocytes. The PAX6 expression was assayed by real-time polymerase chain reaction and Western blot.
Complete aniridia was complicated with horizontal nystagmus, contract, foveal hypoplasia, and microphthalmia. A novel heterozygous c.702_703delinsAT (p.Tyr234*) mutation was found in exon 9 of PAX6, generating a PTC at the homeodomain. There were about 50% reductions of both full-length PAX6 protein and PAX6 mRNA in patient-derived lymphocytes, indicating haploinsufficiency due to nonsense-mediated mRNA decay. Ataluren (PTC124) and geneticin (G418) could induce about 30%-40% translational readthrough. Nonsense suppression therapy restored PAX6 protein to about 65%-70% of unaffected family controls.
Our data expanded the genetic and phenotypic variations of congenital aniridia, and showed the therapeutic effect of nonsense suppression on this disease using patient-derived cells.

Purpose: Congenital aniridia is a kind of panocular disorder characterized by the absence of the iris in both eyes. Paired box 6 (PAX6) gene mutations have been identified as the most common cause of congenital aniridia. The aim of this study was to reveal the genetic defect in PAX6 in a Chinese family with congenital aniridia. Methods: Twelve individuals from a three-generation Chinese family were recruited. All the family members underwent comprehensive ophthalmologic examinations. The entire coding region of PAX6 was amplified by polymerase chain reaction, followed by direct Sanger sequencing. Possible structural and functional changes of protein were predicted by bioinformatic analysis using SIFT and Polyohen-2. Results: Among all the 12 members, four were clinically diagnosed with congenital aniridia. A novel heterozygous mutation c.275G>A (p.R92Q) in exon 6 of PAX6 was identified in all the patients, but not in the unaffected individuals or 1186 healthy subjects. This missense mutation is a G-A transition, converting Arginine (R) to Glutamine (Q) at amino acid 92. The substitution of amino acid in the PAX6 protein changed the local charge density and was predicted to damage the normal protein function. Conclusions: Our study identified a novel mutation of PAX6 responsible for congenital aniridia in a Chinese family, which may contribute to understanding the molecular basis and clinical diagnosis of congenital aniridia.

UNASSIGNED: One prominent pathological feature of congenital aniridia is hypoplasia of the iris, often accompanied by other eye abnormalities. The objective of this study is to identify gene mutations responsible for autosomal dominance in a Chinese family with congenital aniridia, progressive cataracts and mental retardation.
UNASSIGNED: A total of 11 family members, including 6 affected and 5 unaffected individuals were recruited. Whole exome sequencing was performed on the proband and Sanger sequencing was applied to identify the causal mutation in the other family members and control samples.
UNASSIGNED: A heterozygous mutation, c. 112delC (p. Arg38fs) in PAX 6, was identified in the family that was associated with congenital aniridia, progressive cataracts and mental retardation. The mutation was exclusively observed in all affected individuals but not in unaffected family members or unrelated healthy controls without aniridia recruited from Beijing Tongren Hospital. Bioinformatics analysis indicated that the mutation c. 112delC (p. Arg38fs) in PAX 6 affected sugar phosphate backbone construction, leading to half reduction of the full-length protein. Other symptoms such as lens opacity, keratitis, lens dislocation, ciliary body hypoplasia, foveal hypoplasia and mental development retardation were also observed in this family.
UNASSIGNED: These results provided a new insight into the effects of PAX 6 as a mutational hotspot, with a symptom complex that includes congenital aniridia, progressive cataracts and mental retardation. These findings suggested the cognitive treatment of PAX 6-mutated individuals could be considered earlier clinically, combined with medication or surgery of congenital aniridia and progressive cataracts.

Congenital aniridia is a severe autosomal dominant binocular developmental disorder, the primary feature of which is congenital absence or hypoplasia of the iris. PAX6 is the main disease-causing gene of congenital aniridia; inheritance is autosomal dominant. But the current mutations do not fully explain this disorder.
We investigated the mutation profile of genes related in three Chinese families with congenital aniridia through targeted sequencing technology. And we validated the candidate variants by PCR-based Sanger sequencing. Different degree impairments of islet function were observed in the patients with aniridia by carbohydrate tolerance butter and insulin release tests in our study.
We identified four novel mutations of PAX6 from three Chinese families with congenital aniridia, which included heterozygous double mutation c.879_880delCA (p.S294Cfs*46) and c.1124C>G (p.P375R) in Family 1 with three patients, heterozygous frameshift mutation c.308delG (p.P103Qfs*21) in Family 2 with one patient, and c.1192delT (p.S398Pfs*126) in Family 3 with two patients. The three frameshift mutations of PAX6 are co-segregated with the aniridia from controls in the families, but the novel missense mutation is not co-segregated with the phenotype. The frameshift mutations in Family 1 and Family 2 have effects to truncate the protein, but the frameshift mutation in Family 3 will prolong it. We confirmed the phenomenon of male gonadal mosaicism of PAX6 by the sequencing of two linked novel mutations in Family 1. Most of the patients with isolated aniridia have different degrees of islet damage through related clinical tests.
It is therefore noteworthy that we found different types of pathogenic mutation, which have effects of truncating or prolonging protein leaded by frameshift mutation. Our results of this study extended the pathogenic mutation spectrum of PAX6 for congenital aniridia and demonstrated the male germline chimerism by molecular experiments.

BACKGROUND: This study evaluates patients with congenital aniridia and cataract who underwent phacoemulsification, capsular tension ring placement, and foldable intraocular lens implantation.
METHODS: In this prospective case series, 10 patients (17 eyes) underwent cataract surgery via a 3.2 mm clear corneal incision. A continuous circular capsulorhexis with <6 mm diameter was employed. A capsular tension ring and HOYA yellow foldable posterior chamber intraocular lens was implanted. All patients wore color contact lenses postoperatively. Paired t test was used to compare visual acuity, intraocular pressure, and corneal endothelial changes before and after surgery.
RESULTS: A single surgeon performed all surgeries. The best-corrected visual acuity improved from value 1.03 ± 0.27LogMAR preoperatively to value 0.78 ± 0.26LogMAR postoperatively (p = 0.000). The photophobic symptoms improved significantly after surgery. The mean corneal endothelial cell density before and after surgery was 3280 ± 473 cells/mm2 and 2669 ± 850 cells/mm2, respectively (p = 0.006). None of the patients developed corneal endothelial decompensation or secondary glaucoma after surgery.
CONCLUSIONS: Treatment of congenital aniridia and coexistent cataract by phacoemulsification, posterior chamber foldable lens implantation, capsular tension ring placement was safe and effective. Use of colored contact lenses in the postoperative period can reduce photophobic symptoms in this group of patients.
BACKGROUND: ChiCTR-OOC-17011638 (retrospectively registered at 12,June,2017).

OBJECTIVE: To evaluate the efficacy and complications of black diaphragm intra-ocular (BDI) lens implantation in patients with congenital aniridia.
METHODS: Twenty patients underwent BDI lens implantation for the treatment of congenital aniridia from January 1999 to December 2012. Fifteen patients (23 eyes) were enrolled in our study, and the mean follow-up period was 26 months. Patient demographics, clinical evaluations [visual acuity (VA), best-corrected visual acuity (BCVA), intra-ocular pressure measurement (IOP), corneal endothelial cell density (ECD) and ultrasound biomicroscopy (UBM)], complications and treatments were analysed for each patient.
RESULTS: Sixteen eyes (70.1%) had a BCVA better than 20/200 after BDI lens implantation, and photophobia obviously decreased in all patients. Six eyes (26.09%) developed secondary glaucoma after BDI lens implantation, and one eye underwent glaucoma surgery. Corneal decompensation occurred in two eyes (8.70%), one of which was complicated by glaucoma. Two eyes (8.70%) developed visual axis opacity (VAO) after surgery. One patient (4.35%) had limbal stem cell failure, and another patient (4.35%) had an eccentric BDI lens. Intra-ocular pressure measurement elevation and ECD reduction were found after BDI lens implantation.
CONCLUSIONS: Black diaphragm intra-ocular lens implantation can effectively improve VA, decrease photophobia and resolve cosmetic issues in most congenital aniridia eyes. Glaucoma, corneal decompensation and VAO were the major long-term complications of BDI lens implantation in patients with congenital aniridia. All patients should be managed attentively because of high risk of complications and followed long term to achieve favourable outcomes.

We describe the successful treatment in a patient with bilateral congenital aniridia and cataract by insertion of capsular tension rings and IOL.