PAX6 missense mutation in isolated foveal hypoplasia.
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Amino Acid Sequence↗
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Results for “Eye Abnormalities”
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Loss of the SKI proto-oncogene in individuals affected with 1p36 deletion syndrome is predicted by strain-dependent defects in Ski-/- mice.
Experiments involving overexpression of Ski have suggested that this gene is involved in neural tube development and muscle differentiation. In agreement with these findings, Ski-/- mice display a cranial neural tube defect that results in exencephaly and a marked reduction in skeletal muscle mass. Here we show that the penetrance and expressivity of the phenotype changes when the null mutation is backcrossed into the C57BL6/J background, with the principal change involving a switch from a neural tube defect to midline facial clefting. Other defects, including depressed nasal bridge, eye abnormalities, skeletal muscle defects and digit abnormalities, show increased penetrance in the C57BL6/J background. These phenotypes are interesting because they resemble some of the features observed in individuals diagnosed with 1p36 deletion syndrome, a disorder caused by monosomy of the short arm of human chromosome 1p (refs. 6-9). These similarities prompted us to re-examine the chromosomal location of human SKI and to determine whether SKI is included in the deletions of 1p36. We found that human SKI is located at distal 1p36.3 and is deleted in all of the individuals tested so far who have this syndrome. Thus, SKI may contribute to some of the phenotypes common in 1p36 deletion syndrome, and particularly to facial clefting.
Abnormalities, Multiple↗
Loss of eyes in zebrafish caused by mutation of chokh/rx3.
The vertebrate eye forms by specification of the retina anlage and subsequent morphogenesis of the optic vesicles, from which the neural retina differentiates. chokh (chk) mutant zebrafish lack eyes from the earliest stages in development. Marker gene analysis indicates that retinal fate is specified normally, but optic vesicle evagination and neuronal differentiation are blocked. We show that the chk gene encodes the homeodomain-containing transcription factor, Rx3. Loss of Rx3 function in another teleost,medaka, has also been shown to result in an eyeless phenotype. The medaka rx3 locus can fully rescue the zebrafish mutant phenotype. We provide evidence that the regulation of rx3 is evolutionarily conserved, whereas the downstream cascade contains significant differences in gene regulation. Thus, these mutations in orthologous genes allow us to study the evolution of vertebrate eye development at the molecular level.
Animals↗
Psychosocial distress associated with disfiguring eye conditions.
PURPOSE OF STUDY: Visible disfigurement is associated with a range of psychosocial difficulties; however, the problems encountered by patients with eye conditions are under-researched. This study aimed to establish the extent and type of psychosocial distress in this patient population, and to explore the extent to which patients' needs are currently met. METHOD: Standardised measures (anxiety, depression, appearance-related distress, and quality of life) and a semistructured interview (exploring individual experiences and satisfaction with care) were administered to 153 consecutive attenders at outpatient eye clinics in three different hospitals. Responses were analysed using descriptive statistics, multiple regression, and cluster analyses. RESULTS: Between 10 and 49% of the patient sample scored unfavourably on standardised measures in comparison with normative values. Cluster analyses revealed that more distressed patients typically exhibited higher levels of anxiety, depression, social anxiety, self-consciousness, and social avoidance. Quality of life scores were also less favourable. Distressed patients felt less well informed, less involved in their treatment, and less well supported in the clinic setting. Variability within the sample was high; however, the effects of the cause and duration of the condition were not significantly related to distress. Clinic staff identified a variety of constraints to meeting patients' need, including patient numbers, the lack of appropriate training, and the lack of referral possibilities. CONCLUSIONS: A considerable proportion of patients with disfiguring eye conditions experience high levels of psychosocial distress. Several options exist for ways in which patients' needs might more effectively be met within the constraints currently facing care providers.
Adaptation, Psychological↗
The large spectrum of eIF2B-related diseases.
eIF2B (eukaryotic initiation factor 2B) is a GEF (guanine nucleotide-exchange factor) that plays, with its substrate eIF2, a key regulatory role in the translation initiation phase of protein synthesis. The importance of correct control of eIF2 and eIF2B for normal physiology is underlined by the recent involvement of the five genes that encode the five eIF2B subunits in a severe autosomal recessive neurodegenerative disease, described in young children as CACH (childhood ataxia with central nervous system hypomyelination)/VWM (leukoencephalopathy with vanishing white matter) syndrome. The syndrome is characterized by episodes of rapid deterioration during febrile illnesses or following head trauma and symmetrical demyelination of the brain white matter with cavitation aspects, leading to a progressive vanishing of the white matter replaced by CSF (cerebrospinal fluid). However, a wide clinical spectrum has been observed in the 148 patients presently reported, from congenital forms with rapid death to adult-onset forms with slow mental decline and progressive motor dysfunction, sometimes associated with congenital eye abnormalities or ovariodysgenesis. So far, 77 different mutations in each of the five EIF2B genes (EIF2B1-5), encoding subunits eIF2Balpha-epsilon, have been found, with two-thirds affecting the eIF2Bepsilon subunit. The correlation found between the level of GEF activity of eIF2B in the mutated white blood cells and the age at disease onset suggests a direct role of the abnormal translation control in the pathophysiology of the disease.
Ataxia↗
Early embryonic interaction of retinal pigment epithelium and mesenchymal tissue induces conversion of pigment epithelium to neural retinal fate in the silver mutation of the Japanese quail.
The neural retina and retinal pigment epithelium (RPE) diverge from the optic vesicle during early embryonic development. They originate from different portions of the optic vesicle, the more distal part developing as the neural retina and the proximal part as RPE. As the distal part appears to make contact with the epidermis and the proximal part faces mesenchymal tissues, these two portions would encounter different environmental signals. In the present study, an attempt has been made to investigate the significance of interactions between the RPE and mesenchymal tissues that derive from neural crest cells, using a unique quail mutant silver (B/B) as the experimental model. The silver mutation is considered to affect neural crest-derived tissues, including the epidermal melanocytes. The homozygotes of the silver mutation have abnormal eyes, with double neural retinal layers, as a result of aberrant differentiation of RPE to form a new neural retina. Retinal pigment epithelium was removed from early embryonic eyes (before the process began) and cultured to see whether it expressed any phenotype characteristic of neural retinal cells. When RPE of the B/B mutant was cultured with surrounding mesenchymal tissue, neural retinal cells were differentiated that expressed markers of amacrine, cone or rod cells. When isolated RPE of the B/B mutant was cultured alone, it acquired pigmentation and did not show any property characteristic of neural retinal cells. The RPE of wild type quail always differentiated to pigment epithelial cells. In the presence of either acidic fibroblast growth factor (aFGF) or basic FGF (bFGF), the RPE of the B/B mutant differentiated to neural retinal cells in the absence of mesenchymal tissue, but the RPE of wild type embryos only did so in the presence of 10-40 times as much aFGF or bFGF These observations indicate that genes responsible for the B/B mutation are expressed in the RPE as well as in those cells that have a role in the differentiation of neural crest cells. They further suggest that development of the neural retina and RPE is regulated by some soluble factor(s) that is derived from or localized in the surrounding embryonic mesenchyme and other ocular tissues, and that FGF may be among possible candidates.
Animals↗
A case of Peters' anomaly in a springer spaniel.
An 8-week-old springer spaniel presented with a large central corneal opacity of the left globe, which was accompanied by cords of tissue spanning from the iris collarette to the posterior cornea. A posterior cortical cataract was noted in the right eye. At the owner's request the puppy was humanely destroyed, and a necropsy was performed. Upon sectioning the left globe in the vertical plane, a circle of pigmented strands of tissue was observed spanning the anterior chamber from the iris to the posterior aspect of the cornea. The right globe appeared normal when inspected grossly. Histologically, a membrane of pigmented tissue covered the posterior aspect of the broad central corneal leukoma of the left globe. This membrane and the cords traversing the anterior chamber were composed of vascular uveal tissue. Descemet's membrane and the corneal endothelium were reduced or absent in the zone of corneal opacity. Other than the changes associated with cataract, the right globe was histologically normal. The clinical and histological findings in the left globe were identical with those described for Peters>> anomaly in human beings.
Animals↗
Oculo-facio-cardio-dental syndrome: two new cases.
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Adolescent↗
[Hereditary foveal hypoplasia - clinical differentiation].
BACKGROUND: In a family cataract, esotropia and foveal hypoplasia is dominantly transmitted. PATIENTS AND METHOD: Besides the physical examination visual evoked potentials and PAX6 mutation analysis were performed on five of six affected persons and on two who were not. RESULTS: A man of the first generation, deceased before this study, was known to have low vision. His two daughters and their children and grandchildren suffer from cataract, esotropia and foveal hypoplasia. In two cases accompanied by aniridia and atypical iris coloboma respectively. The best visual acuity is 0.5. The VEPs taken of three of the affected people were normal. The PAX6 mutation analysis demonstrated a T to A translocation in the Intron 8 at the position + 2 (= IVS8 + 2T --> A). CONCLUSION: 1) This study confirms that foveal hypoplasia in the so-called isolated form have a similar origin as in aniridia namely PAX6 mutation and that it is a symptom in all cases while the iris anomaly may be variable. 2) In contrast to this foveal hypoplasia in albinism may occur variably in a family while the asymmetry of VEP is a constant finding. 3) Therefore the VEP alone is helpful to differentiate clinically wether a foveal hypoplasia belongs to the albino or to the aniridia group.
Adolescent↗
Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (PEHO syndrome) in two Japanese siblings.
We report on two Japanese siblings (one female and one male) with PEHO syndrome (progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy). They showed profound generalized hypotonia early in infancy and developed infantile spasms with hypsarrhythmia within the first year of life. Abnormal eye movement and visual failure with optic atrophy were also observed early in infancy. Psychomotor development was arrested and serial neuroradiological studies showed slight progressive brain atrophy, dominantly of the brainstem. This is the first case report of PEHO syndrome, other than those dealing with the Finnish population.
Brain↗
[Color and form changes in the iris].
BACKGROUND: The high variability of iris structures can be used for diagnostic purposes. METHODS: An overview of the numerous changes visible at the slit lamp and possible diagnosis. RESULTS: Short description of possible irispathology with hints on pathology and treatment.
Diagnosis, Differential↗
[Eye manifestations of fetal alcohol syndrome].
Alcohol is the most frequent and most important teratogenic agent causing mental and physical retardation in childhood. The alcohol fetal syndrome is characterized by pre- and postnatal growth retardation, hypotonia, hyperactivity, microcephalus, mental retardation and typical craniofacial malformations. The latter includes short palpebral fissures, a poorly developed philtrum, thin upper lip vermillion, short mandibles, a flattened midface structure and dysplastic ears. Ophthalmological signs occur in 90% and include epicanthus, ptosis, myopia, optic nerve hypoplasia and tortuous retinal vessels. Microphthalmus, coloboma and Peters' anomaly have also been described. Five children with alcohol embryopathy are presented. The histopathological findings of the enucleated eye of a 6th child with alcohol embryopathy which was sent to us for examination and which revealed an anterior staphyloma with Peters' anomaly is also described. Ophthalmologists should be aware of alcohol in pregnancy as a preventable cause of eye malformation.
Child, Preschool↗
[Change in the course of blindness in childhood].
In the course of the 20th century there have been major changes in the causes of blindness in childhood. This is illustrated by the example of the 1271 children born between 1885 and 1976 who attended the Bavarian State School for the Blind. The following developments became apparent: Until 1940 the most common cause of blindness, accounting for 25% of the cases, was corneal disease, almost exclusively of infectious origin. This cause has been reduced most, to 2%. There has also been a clear reduction in blindness due to anterior uveitis (mainly due to infection) and chorioretinitis. There were fewer such cases -5% and 3%, respectively. Since the 1960s there have been no further cases of blindness due to ocular injury in children, and no case of sympathetic ophthalmia has occurred since 1950. While the incidence of congenital cataract and buphthalmos has remained constant, they now only lead to blindness in a small proportion of those affected, thanks to improvements in therapy. The incidence of blindness caused by retinal detachment, usually associated with myopia, is also unchanged, though rare (2-3%). The same applies to bilateral retinoblastoma, while the frequency of optic nerve atrophy (20%) and tapetoretinal degeneration (16-19%) has remained both constant and high. There has been a drastic increase in ocular malformations and developmental anomalies. These include retrolental fibroplasia, which was responsible for blindness in 38% of the children born between 1967 and 1976. Overall, there has been a major reduction in the number of blind children in the population since the 1960s and especially since the 1970s.
Blindness↗
Unilateral persistent hyperplastic primary vitreous: course and outcome.
PURPOSE: Improved surgical techniques enable more favorable results in the management of persistent hyperplastic primary vitreous (PHPV). The purpose of our study was to evaluate the outcome of PHPV eyes managed conservatively or after surgery (with or without intraocular lens implantation). METHODS: A total of 89 children (37 boys, 52 girls) with PHPV in one eye (mean follow-up of 6.3 +/- 5.7 years) were included. The children were subgrouped according to treatment modality. Twenty-eight (31.5%) children were managed conservatively (nonoperated). Cataract extraction combined with vitrectomy and removal of embryonic remnants was carried out in 61 eyes (68.5%). Intraocular lenses were implanted in 30 of the operated eyes (pseudophakic) and 31 eyes remained without lens (aphakic). RESULTS: Final evaluated visual acuity in the entire group was 6/15 or better in 12.6% (11 of 87) of the eyes. A total of 11.5% (10 of 87) had a visual acuity of 6/21 to 6/60, 46.0% (40 of 87) obtained 6/90 to light perception and 26 of 87 (29.9%) had no light perception in the involved eye. The rate of no light perception was significantly lower in patients with pseudophakia (10.0%) compared to those with aphakia (43.3%) or nonoperated (37.0%) eyes (P =.009). Intraocular pressure was adequately assessed repeatedly in 72 eyes. High intraocular pressure and glaucomatous changes were observed in 7 of 31 (22.6%) patients with aphakia, 2 of 24(8.3%) patients with pseudophakia and in 2 of 17(11.8%) nonoperated eyes (P =.34). Poor cosmetic outcome was seen in 12 of 31 (38.7%) children with aphakic eyes and 5 of 30 (16.7%) children with pseudophakic eyes (P =.08). Prosthesis or cosmetic shells were needed for 8 of 31 patients with aphakia, for none of the patients with pseudophakia and for 2 of 28 of the nonoperated children (P =.003). CONCLUSION: PHPV eyes have a potential for developing useful vision with favorable cosmetic outcome after surgery. Intraocular lens implantation may be a favorable and beneficial option for the management of children with unilateral PHPV.
Aphakia, Postcataract↗
The many faces of PHACE syndrome.
OBJECTIVES: PHACE is an acronym coined to describe a neurocutaneous syndrome encompassing the following features: posterior fossa brain malformations, large facial hemangiomas, arterial anomalies, cardiac anomalies and aortic coarctation, and eye abnormalities. We evaluated the spectrum of disease and significance of potential underlying brain anomalies among affected children. STUDY DESIGN: The records of 14 patients with PHACE syndrome, evaluated between 1995 and 2000, were retrospectively reviewed. A literature review revealed 116 additional cases. RESULTS: PHACE syndrome represents a spectrum of anomalies, because most affected children have only one extracutaneous manifestation. The syndrome is associated with a high incidence of arterial and structural central nervous system anomalies with secondary neurologic sequelae. The potential for progressive neurovascular disease also exists among those patients with anomalous vasculature. CONCLUSION: PHACE syndrome should be considered in any infant presenting with a large, segmental, plaque-type facial hemangioma. Children at risk should receive careful ophthalmologic, cardiac, and neurologic assessment.
Abnormalities, Multiple↗
Targeted expression of teashirt induces ectopic eyes in Drosophila.
teashirt was initially identified as a gene required for the specification of the trunk segments in Drosophila embryogenesis and encodes a transcription factor with zinc finger motifs. We report here that targeted expression of teashirt in imaginal discs is sufficient to induce ectopic eye formation in non-eye tissues, a phenotype similar to that produced from targeted expression of eyeless, dachshund, and eyes absent. Furthermore, teashirt and eyeless induce the expression of each other, suggesting that teashirt is part of the gene network that functions to specify eye identity.
Animals↗
Ectopic bone morphogenetic proteins 5 and 4 in the chicken forebrain lead to cyclopia and holoprosencephaly.
Proper dorsal-ventral patterning in the developing central nervous system requires signals from both the dorsal and ventral portions of the neural tube. Data from multiple studies have demonstrated that bone morphogenetic proteins (BMPs) and Sonic hedgehog protein are secreted factors that regulate dorsal and ventral specification, respectively, within the caudal neural tube. In the developing rostral central nervous system Sonic hedgehog protein also participates in ventral regionalization; however, the roles of BMPs in the developing brain are less clear. We hypothesized that BMPs also play a role in dorsal specification of the vertebrate forebrain. To test our hypothesis we implanted beads soaked in recombinant BMP5 or BMP4 into the neural tube of the chicken forebrain. Experimental embryos showed a loss of the basal telencephalon that resulted in holoprosencephaly (a single cerebral hemisphere), cyclopia (a single midline eye), and loss of ventral midline structures. In situ hybridization using a panel of probes to genes expressed in the dorsal and ventral forebrain revealed the loss of ventral markers with the maintenance of dorsal markers. Furthermore, we found that the loss of the basal telencephalon was the result of excessive cell death and not a change in cell fates. These data provide evidence that BMP signaling participates in dorsal-ventral patterning of the developing brain in vivo, and disturbances in dorsal-ventral signaling result in specific malformations of the forebrain.
Animals↗
The twisted abdomen phenotype of Drosophila POMT1 and POMT2 mutants coincides with their heterophilic protein O-mannosyltransferase activity.
Walker-Warburg syndrome, caused by mutations in protein O-mannosyltransferase-1 (POMT1), is an autosomal recessive disorder characterized by severe brain malformation, muscular dystrophy, and structural eye abnormalities. As humans have a second POMT, POMT2, we cloned each Drosophila ortholog of the human POMT genes and carried out RNA interference (RNAi) knock-down to investigate the function of these proteins in vivo. Drosophila POMT2 (dPOMT2) RNAi mutant flies showed a "twisted abdomen phenotype," in which the abdomen is twisted 30-60 degrees , similar to the dPOMT1 mutant. Moreover, dPOMT2 interacted genetically with dPOMT1, suggesting that the dPOMTs function in collaboration with each other in vivo. We expressed dPOMTs in Sf21 cells and measured POMT activity. dPOMT2 transferred a mannose to the dystroglycan protein only when it was coexpressed with dPOMT1. Likewise, dPOMT1 showed POMT activity only when coexpressed with dPOMT2, and neither dPOMT showed any activity by itself. Each dPOMT RNAi fly totally reduced POMT activity, despite the specific reduction in the level of each dPOMT mRNA. The expression pattern of dPOMT2 mRNA was found to be similar to that of dPOMT1 mRNA using whole mount in situ hybridization. These results demonstrate that the two dPOMTs function as a protein O-mannosyltransferase in association with each other, in vitro and in vivo, to generate and maintain normal muscle development.
Amino Acid Sequence↗