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At least 19 recordsLinked to original sources
PubMed2000

Black diaphragm aniridia intraocular lens for congenital aniridia: long-term follow-up.

PURPOSE: To present long-term results of implantation of a black diaphragm aniridia intraocular lens (IOL) in eyes with congenital aniridia. SETTING: Eye Hospital, Heinrich-Heine-University, Düsseldorf, Germany. METHODS: Cataract surgery was performed in 19 eyes of 14 patients with congenital aniridia. The black diaphragm aniridia IOL was implanted in front of the capsular bag in the ciliary sulcus. Mean patient age was 30 years (range 10 to 59 years) and mean follow-up, 46 months (range 12 to 84 months). Before surgery, corneal epithelial disorders; corneal pannus; cataract; hypoplasia of the macula, optic nerve, or both; and nystagmus were present in all 19 eyes. Clinically detectable glaucoma was present in 5 eyes. RESULTS: Despite the presence of amblyopia and nystagmus, visual acuity improved in 14 of the 19 eyes. The main postoperative problems were glaucoma deterioration (4 of 19 eyes) or development (4 of 19 eyes), cystoid macular edema (2 of 11 eyes), chronic endothelial cell loss (3 of 11 eyes), and progression of corneal epithelial disorders (4 of 19 eyes). Glaucoma was controlled by medical or surgical therapy in all patients. Intraocular lens explantation was performed in 2 eyes with glaucoma. CONCLUSION: Implantation of the black diaphragm aniridia IOL improved visual acuity in the majority of patients with a variety of endogenous problems in addition to aniridia.

Adolescent↗
PubMed2001

Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia.

Aniridia is a severe eye disease characterized by iris hypoplasia; both sporadic cases and familial cases with an autosomal dominant inheritance exist. Mutations in the PAX6 gene have been shown to be the genetic cause of the disease. Some of the sporadic cases are caused by large chromosomal deletions, some of which also include the Wilms tumor gene (WAGR syndrome), resulting in an increased risk of developing Wilms tumor. Based on the unique registration of both cancer and aniridia cases in Denmark, we have made the most accurate risk estimate to date for Wilms tumor in sporadic aniridia. We have found that patients with sporadic aniridia have a relative risk of 67 (confidence interval: 8.1-241) of developing Wilms tumor. Among patients investigated for mutations, Wilms tumor developed in only two patients out of 5 with the Wilms tumor gene (WT1) deleted. None of the patients with smaller chromosomal deletions or intragenic mutations were found to develop Wilms tumor. Our observations suggest a smaller risk for Wilms tumor than previous estimates, and that tumor development requires deletion of WT1. We report a strategy for the mutational analysis of aniridia cases resulting in the detection of mutations in 68% of sporadic cases and 89% of familial cases. We also report four novel mutations in PAX6, and furthermore, we have discovered a new alternatively spliced form of PAX6.

Alternative Splicing↗
PubMed2004

Black diaphragm aniridia intraocular lens for aniridia and albinism.

BACKGROUND: Our aim was to assess the safety and efficacy of primary and secondary implantation of a black diaphragm aniridia intraocular lens (IOL) in patients that lacked a complete iris diaphragm. METHODS: This was a retrospective non-comparative study of six eyes in five patients with iris defects. The causes of such defects included congenital aniridia, traumatic aniridia, and oculocutaneous albinism. Three eyes underwent primary implantations of a black diaphragm IOL, and three eyes were given secondary implantations. The visual acuity, subjective severity of glare, postoperative anatomical outcome and any intraoperative or postoperative complications were reviewed. RESULTS: The mean follow-up period was 20.6 months (range 3-29 months). All patients showed stable or improvement in best-corrected visual acuity postoperatively. Glare and photophobia had improved subjectively in all patients after implantation of the black diaphragm IOL. Intraoperative complication included one case of hyphaema and iris damage during insertion of the IOL. Postoperative complications included intraocular inflammation with choroidal detachment, secondary glaucoma, and persistent epithelial defect after surgery. None of the patients developed decentration of IOL after surgery. CONCLUSION: The black diaphragm aniridia IOL is useful in the management of the condition in patients with iris deficiency including oculocutaneous albinism. Intraoperative and postoperative complications are not uncommon, and patients should be monitored carefully in the perioperative period.

Adult↗
PubMed1994

Paired box mutations in familial and sporadic aniridia predicts truncated aniridia proteins.

Aniridia, an autosomal dominant ocular disorder characterized by iris hypoplasia, results from mutations in the PAX6 gene, which encodes paired box and homeobox motifs. In this report we describe five new mutations in the paired box region of the human PAX6 gene that are associated with aniridia. The paired box mutations that we detected were in both familial (three) and sporadic (two) cases. All five mutations predict truncated PAX6 proteins. Our study indicates that early premature translational termination mutations in the PAX6 gene result in haploinsufficiency and generate the aniridia phenotype.

Amino Acid Sequence↗
PubMed1992

Resolution of the two loci for autosomal dominant aniridia, AN1 and AN2, to a single locus on chromosome 11p13.

Two distinct loci have been proposed for aniridia; AN1 for autosomal dominant aniridia on chromosome 2p and AN2 for the aniridia in the WAGR contiguous gene syndrome on chromosome 11p13. In this report, the kindred segregating for autosomal dominant aniridia, which suggested linkage to acid phosphatase-1 (ACP1) and led to the assignment of the AN1 locus on chromosome 2p, has been updated and expanded. Linkage analysis between the aniridia phenotype and ACP1 does not support the original linkage results, excluding linkage up to theta = 0.17 with Z = -2. Tests for linkage to other chromosome 2p markers. APOB, D2S71, D2S5, and D2S1, also excluded linkage to aniridia. Markers that have been isolated from the chromosome 11p13 region were then analyzed in this aniridia family. Two RFLPs at the D11S323 locus give significant evidence for linkage. The PvuII polymorphism detected by probe p5S1.6 detects no recombinants, with a maximum lod score of Z = 6.97 at theta = 0.00. The HaeIII polymorphism detected by the probe p5BE1.2 gives a maximum lod score of Z = 2.57 at theta = 0.00. Locus D11S325 gives a lod score of Z = 1.53 at theta = 0.00. These data suggest that a locus for aniridia (AN1) on chromosome 2p has been misassigned and that this autosomal dominant aniridia family is segregating for an aniridia mutation linked to markers in the 11p13 region.

Alkaline Phosphatase↗
PubMed2004

Ocular and nonocular findings in patients with aniridia.

BACKGROUND: Aniridia typically appears as a familial condition with autosomal dominant inheritance but can present as an isolated disease or sporadically in association with several syndromes. In this report we describe the various ocular manifestations of aniridia as well as the association of familial aniridia with two different ocular and systemic abnormalities present across three generations in two different families. METHODS: Descriptive case series of 33 patients (66 eyes) with aniridia. A full eye examination was performed at the beginning of the study, including past medical history, family history and type of inheritance, assessment for fixation pattern and presence of nystagmus, visual acuity testing, refraction, slit-lamp examination, gonioscopy, fundus examination with pupil dilation and anterior segment photography; additional glaucoma testing was done if the patient had high intraocular pressure. Patients were followed for at least 2 years. The interval between follow-up visits, which included gonioscopy and fundus examination with pupil dilation, depended on the findings in each case. A urology consultation was requested in all sporadic aniridia cases; consultations in psychiatry and gynecology were requested on the basis of the medical history or clinical suspicion during the ophthalmologic examination. RESULTS: Ten patients (30%) had sporadic aniridia, with no previous family history; Wilms' tumour did not develop in any of them during the follow-up period. In the autosomal dominant group, ocular and systemic findings present in combination with aniridia were observed in 20 patients in the two families. Family I had aniridia and developmental delay or behavioural disorders in three generations as well as high myopia (greater than 6.00 dioptres) in all affected adults. Family 2 presented a wide phenotypic variability of aniridia with myopia in three generations. Open-angle glaucoma developed in three young adults in this family, and two members were found to have gynecologic abnormalities (hypoplastic uterus and imperforate vagina). Myopia was the most prevalent refractive error (64%) in the 33 patients. Refractive correction significantly improved the visual acuity in half of these cases. Glaucoma was present in 10 patients (30%) and was the main cause of vision loss, provoking blindness in two cases (6%). Affected patients manifested progressive angle closure or presented with open-angle glaucoma. INTERPRETATION: Ophthalmologists should consider aniridia in patients with unusual iris malformations. Examination of family members may be key in making the diagnosis. Any refractive error should be corrected, as this may improve vision. All aniridic patients should be screened regularly for glaucoma, as this condition may occur at any age and can lead to permanent vision loss. Systemic and ocular associations should be considered as they may present in combination with anirida. In our series, developmental delay or behavioural disorders and myopia were associated conditions.

Adolescent↗
PubMed1982

Wilms's tumour and aniridia: clinical and cytogenetic features.

A survey carried out to detect children with aniridia/Wilms's tumour syndrome identified 8 living and 3 dead children. The incidence of aniridia was found to be 1 in 43 among Wilms's tumour patients in the UK. The clinical features included complete bilaterial aniridia, cataracts, glaucoma, mental retardation, hyperkinesis, hypospadias, and undescended testes. A high incidence of bilateral tumours (36%), male sex, presentation at a young age, and advanced maternal age appeared to be associated with the syndrome. The 8 living children each had a deletion on the short arm of chromosome 11. In contrast, although 2 patients with sporadic aniridia without Wilms's tumour had other malformations, neither had genitourinary anomalies, and the only additional problems in patients with familial aniridia were cataracts. Among 49 children with Wilms's tumour without aniridia ony one had bilateral tumours. No chromosome abnormalities were detected in patients with familial aniridia, nor were they detected in patients with Wilms's tumour without aniridia or in those with sporadic aniridia without Wilms's tumour. While many infants with the Wilms's tumour/aniridia syndrome are clinically diagnosable at birth, chromosome analysis using the elongated chromosome method is especially valuable to confirm the diagnosis in girls with sporadic aniridia and in boys who lack the genitourinary malformations. The presence of an 11p13 deletion confirms the diagnosis of the Wilms's tumour/aniridia syndrome and indicates a very high risk for the development of Wilms's tumour.

Child, Preschool↗
PubMed2005

Central corneal thickness in patients with congenital aniridia.

PURPOSE: To compare the mean central corneal thickness (CCT) in patients with congenital aniridia to that of a group of age-matched control subjects. The findings of specular and confocal microscopy in a patient with aniridia are discussed. METHODS: The mean values of five consecutive pachymetry measurements of patients with aniridia and control subjects were used for analysis. Statistical analysis was performed with a Mann-Whitney rank sum test. Specular microscopy was performed on one patient with aniridia using a Konan Specular Microscope Noncon ROBO CA (Hyogo, Japan). Confocal microscopy through focusing was performed with the Tandem Scanning Confocal Microscope (Reston, VA). RESULTS: Mean CCT measured 691.8 +/- 75.4 mum for patients with aniridia (16 eyes of 10 patients) and 548.2 +/- 21.2 mum for control subjects (P < 0.001). Specular microscopy in a patient with aniridia showed normal endothelial cell counts and structure. Confocal microscopy through focusing of this patient showed normal-appearing keratocytes and a thick corneal stroma. CONCLUSIONS: Patients with congenital aniridia have significantly thicker corneas than do age-matched control subjects. This difference can have important implications for the treatment of those patients who develop secondary glaucoma. The increased CCT in patients with aniridia is not a result of endothelial dysfunction but appears to be the result of the production of a thickened but otherwise healthy cornea by the mutated PAX6 gene.

Adolescent↗
PubMed1995

Three novel aniridia mutations in the human PAX6 gene.

Aniridia (iris hypoplasia) is an autosomal dominant congenital disorder of the eye. Mutations in the human aniridia (PAX6) gene have now been identified in many patients from various ethnic groups. In the study reported here we describe PAX6 mutations in one sporadic and five familial cases with aniridia. Of the four different mutations identified, one was identical to a previously reported mutation (C-->T transition at codon 240), and three were novel: two in the glycine-rich region and one in the proline/serine/threonine-rich (PST) region. One PAX6 mutation found in the PST region was associated with cataracts in an aniridia family. Another splice mutation in the PST domain occurred in an aniridia patient with anosmia (inability to smell). The six new aniridia cases reported here have mutations predicted to generate incomplete PAX6 proteins. These results support the theory that human aniridia is caused by haploinsufficiency of PAX6.

Adult↗
PubMed1993

Detection of a cryptic paracentric inversion within band 11p13 in familial aniridia by fluorescence in situ hybridization.

We report the first familial case of dominantly inherited aniridia with a cryptic inversion within band 11p13. High-resolution chromosome analysis gave a suspicion of a tiny constitutional aberration around band 11p13 and fluorescence in situ hybridization using 11p cosmids successfully confirmed that the aniridia patients of this family have an inversion within band 11p13. The distal breakpoint of the inversion is telomeric to a candidate aniridia gene (AN2) and suggests that more genes might be involved in the etiology of aniridia. In situ hybridization is a powerful tool to detect cryptic rearrangements in sporadic or familial patients with aniridia. This family indicated the importance of careful observation of the 11p13 region of aniridia patients, even if the aniridia was autosomal dominantly inherited.

Adult↗
PubMed2004

Ultrasound biomicroscopic findings in aniridia.

PURPOSE: To describe the ultrasound biomicroscopic features of eyes with aniridia. DESIGN: Observational case series. METHODS: Nineteen eyes of 10 patients with aniridia (six males and four females) ranging in age from 3 months to 53 years (21.0 +/- 16.4, mean +/- SD), and 50 normal subjects (30 men and 20 women) ranging from 16 to 56 years (31.1 +/- 13.2) were evaluated. Ultrasound biomicroscopic findings were recorded in the 3-, 6-, 9-, and 12-o'clock directions. Adult patients (aged 16 years or older) with aniridia were compared with the age-matched controls. RESULTS: Ultrasound biomicroscopy (UBM) detected extremely tiny irises in all eyes with aniridia. The eyes with aniridia showed significantly smaller values than the controls in ciliary body length (4.49 +/- 0.63 versus 5.79 +/- 0.44 mm, P <.001, unpaired Student t test), ciliary body thickness (0.75 +/- 0.17 versus 1.24 +/- 0.22 mm, P <.001), iris root thickness (0.47 +/- 0.14 versus 0.61 +/- 0.07 mm, P <.001), scleral-ciliary process angle (31.7 +/- 3.26 versus 43.1 +/- 4.48 degree, P <.001), and anterior chamber depth (1.99 +/- 0.43 versus 2.94 +/- 0.34 mm, P <.001). In the aniridia eyes, there was a significantly positive correlation between iris thickness and ciliary body thickness (Pearson r = 0.829, P =.001). CONCLUSION: Ultrasound biomicroscopic imaging demonstrated that not only iris hypoplasia but also ciliary body hypoplasia exist in aniridia. Anterior inclination of the ciliary process was also found, which was thought to be at least partly responsible for the shallow anterior chamber.

Adolescent↗
PubMed2005

Evolving concepts on the pathogenic mechanisms of aniridia related keratopathy.

Heterozygosity for PAX6 deficiency (PAX6+/-) results in aniridia. Corneal changes in aniridia-related keratopathy (ARK) include corneal vascular pannus formation, conjunctival invasion of the corneal surface, corneal epithelial erosions and epithelial abnormalities, which eventually result in corneal opacity and contribute to visual loss. Corneal changes in aniridia have been attributed to congenital deficiency of corneal limbal stem cells. The aim of this paper is to review the potential mechanisms that may underlie the pathogenesis of aniridia related keratopathy. Current evidence, based on clinical observations and an animal model of aniridia suggest that the proliferative potential of the corneal limbal stem cells may not primarily be impaired. The corneal changes in aniridia may be related to an abnormality within the limbal stem cell niche. The mechanisms underlying progressive corneal pathology in aniridia appear multi-factorial and include: (1) abnormal corneal healing responses secondary to anomalous extracellular matrix metabolism; (2) abnormal corneal epithelial differentiation leading to fragility of epithelial cells; (3) reduction in cell adhesion molecules in the PAX6 heterozygous state, rendering the cells susceptible to natural shearing forces; and (4) conjunctival and corneal changes leading to the presence of cells derived from conjunctiva on the corneal surface.

Animals↗
PubMed1993

PAX6 mutations in aniridia.

Aniridia is a congenital malformation of the eye, chiefly characterised by iris hypoplasia, which can cause blindness. The PAX6 gene was isolated as a candidate aniridia gene by positional cloning from the smallest region of overlap of aniridia-associated deletions. Subsequently PAX6 intragenic mutations were demonstrated in Smalleye, a mouse mutant which is an animal model for aniridia, and six human aniridia patients. In this paper we describe four additional PAX6 point mutations in aniridia patients, both sporadic and familial. These mutations highlight regions of the gene which are essential for normal PAX6 function. In addition, the frequency at which we have found PAX6 mutations suggests that lesions in PAX6 will account for most cases of aniridia.

Amino Acid Sequence↗
PubMed2002

PAX6 mutation as a genetic factor common to aniridia and glucose intolerance.

A paired homeodomain transcription factor, PAX6, is a well-known regulator of eye development, and its heterozygous mutations in humans cause congenital eye anomalies such as aniridia. Because it was recently shown that PAX6 also plays an indispensable role in islet cell development, a PAX6 gene mutation in humans may lead to a defect of the endocrine pancreas. Whereas heterozygous mutations in islet-cell transcription factors such as IPF1/IDX-1/STF-1/PDX-1 and NEUROD1/BETA2 serve as a genetic cause of diabetes or glucose intolerance, we investigated the possibility of PAX6 gene mutations being a genetic factor common to aniridia and diabetes. In five aniridia and one Peters' anomaly patients, all of the coding exons and their flanking exon-intron junctions of the PAX6 gene were surveyed for mutations. The results of direct DNA sequencing revealed three different mutations in four aniridia patients: one previously reported type of mutation and two unreported types. In agreement with polypeptide truncation and a lack of the carboxyl-terminal transactivation domain in all of the mutated PAX6 proteins, no transcriptional activity was found in the reporter gene analyses. Oral glucose tolerance tests revealed that all of the patients with a PAX6 gene mutation had glucose intolerance characterized by impaired insulin secretion. Although we did not detect a mutation within the characterized portion of the PAX6 gene in one of the five aniridia patients, diabetes was cosegregated with aniridia in her family, and a single nucleotide polymorphism in intron 9 of the PAX6 gene was correlated with the disorders, suggesting that a mutation, possibly located in an uncharacterized portion of the PAX6 gene, can explain both diabetes and aniridia in this family. In contrast, the patient with Peters' anomaly, for which a PAX6 gene mutation is a relatively rare cause, showed normal glucose tolerance (NGT) and did not show a Pax6 gene mutation. Taken together, our present observations suggest that heterozygous mutations in the PAX6 gene can induce eye anomaly and glucose intolerance in individuals harboring these mutations.

Adolescent↗
PubMed2005

Mutation analysis of PAX6 gene in a large Chinese family with aniridia.

BACKGROUND: Mutations in PAX6 gene have been shown to be the genetic cause of aniridia, which is a severe panocular eye disease characterised by iris hypoplasia. However, there is no study to do genetic analysis of aniridia, although there are several case reports in China. Here, we describe a mutation analysis of PAX6 in a large Chinese family with aniridia. METHODS: Genomic DNA from venous blood samples was prepared. Haplotype analysis was performed with two genetic markers (D11S904 and D11S935). Fourteen exons of the PAX6 gene were amplified from genomic DNA. Polymerase chain reaction (PCR) products of each exon were analysed by single strand conformational polymorphism (SSCP). The PCR products having an abnormal pattern were sequenced to confirm the mutation. RESULTS: Significant evidence for allele sharing in affected patients was detected suggesting that PAX6 mutation links to aniridia in this family. An extra band corresponding to exon 9 in PAX6 was found by single strand conformational polymorphism analysis in all the aniridia patients in this family, but not detected in the unaffected members. A mutation of C to T was detected by sequencing at the nucleotide 1080 that converts the Arg codon (CGA) to the termination codon (TGA). CONCLUSIONS: Aniridia is caused by a nonsense mutation of PAX6 gene in the large Chinese kindred. Genetic test is important to prevent the transmission of aniridia to their offsprings in the kindred by prenatal diagnosis.

Aniridia↗