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In children with Down syndrome (DS) development of visual, motor and cognitive functions is atypical. It is unknown whether the visual impairments in children with DS aggravate their lag in cognitive development. Visual impairment and developmental lags in adaptive behaviour and executive functions were assessed in 104 children with DS, 2–16 years, by comparing their adaptive behaviour, executive functions and visual acuity (distant and near) scores against published age-matched norm scores of typically developing children. Associations between these lags were explored. Mean (± SEM) differences to age-matched norms indicated reduced performance in DS: Vineland Screener questionnaire, − 63 ± 3.8 months; task-based Minnesota Executive Function Scale (MEFS), − 46.09 ± 2.07 points; BRIEF-P questionnaire, 25.29 ± 4.66 points; BRIEF parents’ and teachers’ questionnaire, 17.89 ± 3.92 points and 40.10 ± 3.81 points; distant and near visual acuity, 0.51 ± 0.03 LogMAR and 0.63 ± 0.03 LogMAR (near − 0.11 ± 0.04 LogMAR poorer than distant). Adaptive behaviour (Vineland-S) correlated with the severity of visual impairment (r = − 0.396). Children with DS are severely impaired in adaptive behaviour, executive functions and visual acuities (near visual acuity more severely impaired than distant visual acuity). Larger impairment in adaptive behaviour is found in children with larger visual impairment. This supports the idea that visual acuity plays a role in adaptive development.

Contains fulltext : 244138.pdf (Publisher’s version ) (Open Access) There is evidence that a pen-and-paper training based on perceptual learning principles improves near visual acuity in young children with visual impairment. The aim of the present study is to measure specificity and retention of its training effects during one year. Sixteen visually impaired children aged 4-8 years were divided in two age- and acuity-matched groups: an early (n = 9) and late treatment group (n = 7). Training consisted of 12 sessions (2× per week for 6 weeks). Studied variables were uncrowded and crowded binocular near visual acuity (40 cm), distance visual acuity (3.0 m) and fine motor skills (Beery VMI, subtest Motor Control). In the early treatment group, we measured at 0 months (pre-training), at 2 months (post-training), at 8 months (6 months post-training) and at 14 months (12 months post-training) since inclusion. In the late treatment group, three pre-training measurements were performed at 0, 2 and 8 months, and two measurements at 0 and 6 months post-training. In the short term, training improved uncrowded and crowded near visual acuity at 0.4 m by 0.13 ± 0.03 and 0.09 ± 0.03 logMAR, respectively (mean ± SEM). Training did not affect distance acuities or Beery scores. Learning effects on uncrowded and crowded near visual acuities remained intact 6-12 months after training. We conclude that the pen-and-paper training specifically improves near visual acuities but does not transfer to distance acuities or fine motor skills. Improvements in near visual acuity are retained over time, bolstering its clinical value.

Contains fulltext : 225467.pdf (Publisher’s version ) (Closed access) PURPOSE: To study the disease course of RPE65-associated inherited retinal degenerations (IRDs) as a function of the genotype, define a critical age for blindness, and identify potential modifiers. METHODS: Forty-five patients with IRD from 33 families with biallelic RPE65 mutations, 28 stemming from a genetic isolate. We collected retrospective data from medical charts. Coexisting variants in 108 IRD-associated genes were identified with Molecular Inversion Probe analysis. RESULTS: Most patients were diagnosed within the first years of life. Daytime visual function ranged from near-normal to blindness in the first four decades and met WHO criteria for blindness for visual acuity and visual field in the fifth decade. p.(Thr368His) was the most common variant (54%). Intrafamilial variability and interfamilial variability in disease severity and progression were observed. Molecular Inversion Probe analysis confirmed all RPE65 variants and identified one additional variant in LRAT and one in EYS in two separate patients. CONCLUSION: All patients with RPE65-associated IRDs developed symptoms within the first year of life. Visual function in childhood and adolescence varied but deteriorated inevitably toward blindness after age 40. In this study, genotype was not predictive of clinical course. The variance in severity of disease could not be explained by double hits in other IRD genes.

PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene, and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: STUDY POPULATION: Total of 302 patients with IRD. from 2 ophthalmogenetic centers in the Netherlands. REFERENCE POPULATION: Population-based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell-related dystrophies were associated with the highest risk of SE high myopia 239.7; odds ratio (OR) mild hyperopia 263.2, both P

Contains fulltext : 168142.pdf (Publisher’s version ) (Closed access) PURPOSE: This study aimed to examine the controllability of cylinder-shaped and dome-shaped magnifiers in young children with visual impairment. METHODS: This study investigates goal-directed arm movements in low-vision aid use (stand and dome magnifier-like object) in a group of young children with visual impairment (n = 56) compared to a group of children with normal sight (n = 66). Children with visual impairment and children with normal sight aged 4-8 years executed two types of movements (cyclic and discrete) in two orientations (vertical or horizontal) over two distances (10 cm and 20 cm) with two objects resembling the size and shape of regularly prescribed stand and dome magnifiers. RESULTS: The visually impaired children performed slower movements than the normally sighted children. In both groups, the accuracy and speed of the reciprocal aiming movements improved significantly with age. Surprisingly, in both groups, the performance with the dome-shaped object was significantly faster (in the 10 cm condition and 20 cm condition with discrete movements) and more accurate (in the 20 cm condition) than with the stand-shaped object. CONCLUSION: From a controllability perspective, this study suggests that it is better to prescribe dome-shaped than cylinder-shaped magnifiers to young children with visual impairment. 7 p.

Purpose We determined the latencies of orienting responses during a preferential looking task in children with normal vision and in children with visual impairments between 6 and 12 years old, and assessed the feasibility of scoring grating detection in these populations with video‐based eye tracking. Methods Children performed a computerized preferential looking test, while a remote eye tracker measured the children's eye movements. The stimuli consisted of a 2 × 2 grid, with three uniform grey fields and one target field consisting of a black‐and‐white square wave grating. The grating was presented randomly at one of the four locations. The spatial frequencies (1.05, 2.11 and 7.02 cyc/deg) were randomly interleaved, with 10 trials per spatial frequency. Three different methods were used to score the accuracy of the responses: (1) primary saccade ends on target, (1) gaze 50% of the presentation time on target, and (3) a combination of method 1 and 2 (i.e. primary saccade ends on target, and/or gaze 50% of the presentation time on target). Results The combined scoring method was most reliable to determine whether children could resolve the gratings. Children with visual impairments had significantly lower accuracies than children with normal vision with all three scoring methods. In addition, saccade latencies decreased with age and were significantly longer (62 ± 15 ms) in children with visual impairments. Conclusion The use of eye tracking to assess grating detection with a preferential looking task in clinical populations provides valuable additional information, including objective detection measures and developmental delays in saccade latencies.

Previous research has shown an age-related decline in Useful Field of View (UFOV) test performance, which measures the duration required to extract relevant information from a scene in three subtasks. However, these results are mostly based on data that may have been confounded by (age-related) ocular diseases. We examined UFOV performance in subjects aged 19.5 to 70.3 years to investigate how UFOV performance changes throughout adulthood. All subjects underwent a thorough ophthalmological examination to exclude ocular disorders. We also examined some elementary visual functions, i.e., near and far visual acuity, crowding and contrast sensitivity. We investigated whether these functions were related to age and whether they could explain a possible age-related decline in UFOV performance. The subjects (n = 41) performed very well on almost every measure and reached far better UFOV and visual acuity scores than those reported by other studies that relied on self-reported absence of ocular pathology. We did not find significant relationships between age and any of the elementary visual functions or the first two UFOV subtasks (R2UFOV1 = 0.03, p = 0.25; R2UFOV2 = 0.07, p = 0.10). However, we found an age-related decline in performance on the third UFOV subtask (R2UFOV3 = 0.36, p < 0.001), which was unrelated to performance on the elementary visual function tasks. Our results show that performance on the first two UFOV subtasks as well as central elementary visual functions may remain high in the absence of obvious ophthalmological pathology.

Purpose Many visually guided tasks require rapid perception of visual details, but how fast children can discern foveal stimuli and how this ability improves with age are still unknown. To fill this gap, we tested normally sighted children between 5 and 12 years of age with a combined symbol-discrimination reaction-time test. Methods Children (n = 94) had to indicate, as fast and accurately as possible, the orientation of a Landolt C symbol (90 trials). Task difficulty was manipulated by varying symbol size (-0.43 to 1.09 logMAR at 5 m). The resulting reaction times were analyzed with a drift-diffusion model. Reaction times on a visual and auditory detection task were measured to assess the contribution of other factors, such as delays in stimulus detection and executing the motor response. Results Detection and discrimination were significantly faster in older children. Five-year-olds needed ∼440 ms for visual detection and ∼980 ms for discrimination of the largest symbols while 12-year-olds needed only ∼250 ms and ∼500 ms for this. The extra time needed for discrimination compared with detection decreased with age. The decrease in reaction time with increasing optotype size was also age-dependent and indicated an increase in sensitivity with age. Despite the time pressure, acuity thresholds were normal (within the EN ISO-8597 standard). Conclusions Our data revealed substantial developmental improvements in visual discrimination speed, which suggests that an important optimization takes place in the developing visual system of 5- to 12-year-old children. Since the speed-acuity test allows for quick and reliable assessment of visual recognition acuity and speed, it may be useful in clinical testing too.

Item does not contain fulltext Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subclass of congenital disorders of glycosylation. Here we performed whole-exome sequencing in an individual with cerebral visual impairment (CVI), intellectual disability (ID), and factor XII deficiency and revealed compound heterozygous variants in PGAP1, c.274_276del (p.(Pro92del)) and c.921_925del (p.(Lys308Asnfs*25)). Subsequently, PGAP1-deficient Chinese hamster ovary (CHO)-cell lines were transfected with either mutant or wild-type constructs and their sensitivity to phosphatidylinositol-specific phospholipase C (PI-PLC) treatment was measured. The mutant constructs could not rescue the PGAP1-deficient CHO cell lines resistance to PI-PLC treatment. In addition, lymphoblastoid cell lines (LCLs) of the affected individual showed no sensitivity to PI-PLC treatment, whereas the LCLs of the heterozygous carrier parents were partially resistant. In conclusion, we report novel PGAP1 variants in a boy with CVI and ID and a proven functional loss of PGAP1 and show, to our knowledge, for the first time this genetic association with CVI.

Item does not contain fulltext BACKGROUND: Cerebral visual impairment (CVI) is a disorder in projection and/or interpretation of the visual input in the brain and accounts for 27% of the visually impaired children. AIM: A large cohort of patients with CVI was investigated in order to ascertain the relevance of chromosomal aberrations in the etiology of this disorder. METHODS: 607 patients with CVI and a visual acuity

Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous disorder characterized by abnormal vascularization of the peripheral retina, which can result in retinal detachment and severe visual impairment. In a large Dutch FEVR family, we performed linkage analysis, exome sequencing, and segregation analysis of DNA variants. We identified putative disease-causing DNA variants in proline-alanine-rich ste20-related kinase (c.791dup; p.Ser265ValfsX64) and zinc finger protein 408 ( ZNF408 ) (c.1363C>T; p.His455Tyr), the latter of which was also present in an additional Dutch FEVR family that subsequently appeared to share a common ancestor with the original family. Sequence analysis of ZNF408 in 132 additional individuals with FEVR revealed another potentially pathogenic missense variant, p.Ser126Asn, in a Japanese family. Immunolocalization studies in COS-1 cells transfected with constructs encoding the WT and mutant ZNF408 proteins, revealed that the WT and the p.Ser126Asn mutant protein show complete nuclear localization, whereas the p.His455Tyr mutant protein was localized almost exclusively in the cytoplasm. Moreover, in a cotransfection assay, the p.His455Tyr mutant protein retains the WT ZNF408 protein in the cytoplasm, suggesting that this mutation acts in a dominant-negative fashion. Finally, morpholino-induced knockdown of znf408 in zebrafish revealed defects in developing retinal and trunk vasculature, that could be rescued by coinjection of RNA encoding human WT ZNF408 but not p.His455Tyr mutant ZNF408. Together, our data strongly suggest that mutant ZNF408 results in abnormal retinal vasculogenesis in humans and is associated with FEVR.

Contains fulltext : 116604.pdf (Publisher’s version ) (Open Access) PURPOSE. This study investigated whether visual perceptual learning can improve near visual acuity and reduce foveal crowding effects in four-to nine-year-old children with visual impairment. METHODS. Participants were 45 children with visual impairment and 29 children with normal vision. Children with visual impairment were divided into three groups: a magnifier group (n = 12), a crowded perceptual learning group (n = 18), and an uncrowded perceptual learning group (n = 15). Children with normal vision also were divided in three groups, but were measured only at baseline. Dependent variables were single near visual acuity (NVA), crowded NVA, LH line 50% crowding NVA, number of trials, accuracy, performance time, amount of small errors, and amount of large errors. Children with visual impairment trained during six weeks, two times per week, for 30 minutes (12 training sessions). RESULTS. After training, children showed significant improvement of NVA in addition to specific improvements on the training task. The crowded perceptual learning group showed the largest acuity improvements (1.7 logMAR lines on the crowded chart, P < 0.001). Only the children in the crowded perceptual learning group showed improvements on all NVA charts. CONCLUSIONS. Children with visual impairment benefit from perceptual training. While task-specific improvements were observed in all training groups, transfer to crowded NVA was largest in the crowded perceptual learning group. To our knowledge, this is the first study to provide evidence for the improvement of NVA by perceptual learning in children with visual impairment. 9 p.

Item does not contain fulltext PURPOSE: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an autosomal-dominant disorder characterized by optic atrophy and intellectual disability caused by loss-of-function mutations in NR2F1. We report 20 new individuals with BBSOAS, exploring the spectrum of clinical phenotypes and assessing potential genotype-phenotype correlations. METHODS: Clinical features of individuals with pathogenic NR2F1 variants were evaluated by review of medical records. The functional relevance of coding nonsynonymous NR2F1 variants was assessed with a luciferase assay measuring the impact on transcriptional activity. The effects of two start codon variants on protein expression were evaluated by western blot analysis. RESULTS: We recruited 20 individuals with novel pathogenic NR2F1 variants (seven missense variants, five translation initiation variants, two frameshifting insertions/deletions, one nonframeshifting insertion/deletion, and five whole-gene deletions). All the missense variants were found to impair transcriptional activity. In addition to visual and cognitive deficits, individuals with BBSOAS manifested hypotonia (75%), seizures (40%), autism spectrum disorder (35%), oromotor dysfunction (60%), thinning of the corpus callosum (53%), and hearing defects (20%). CONCLUSION: BBSOAS encompasses a broad range of clinical phenotypes. Functional studies help determine the severity of novel NR2F1 variants. Some genotype-phenotype correlations seem to exist, with missense mutations in the DNA-binding domain causing the most severe phenotypes.Genet Med 18 11, 1143-1150.

Contains fulltext : 168038.pdf (Publisher’s version ) (Open Access) PURPOSE: Perceptual learning improves visual acuity and reduces crowding in children with infantile nystagmus (IN). Here, we compare reading performance of 6- to 11-year-old children with IN with normal controls, and evaluate whether perceptual learning improves their reading. METHODS: Children with IN were divided in two training groups: a crowded training group (n = 18; albinism: n = 8; idiopathic IN: n = 10) and an uncrowded training group (n = 17; albinism: n = 9; idiopathic IN: n = 8). Also 11 children with normal vision participated. Outcome measures were: reading acuity (the smallest readable font size), maximum reading speed, critical print size (font size below which reading is suboptimal), and acuity reserve (difference between reading acuity and critical print size). We used multiple regression analyses to test if these reading parameters were related to the children's uncrowded distance acuity and/or crowding scores. RESULTS: Reading acuity and critical print size were 0.65 +/- 0.04 and 0.69 +/- 0.08 log units larger for children with IN than for children with normal vision. Maximum reading speed and acuity reserve did not differ between these groups. After training, reading acuity improved by 0.12 +/- 0.02 logMAR and critical print size improved by 0.11 +/- 0.04 logMAR in both IN training groups. The changes in reading acuity, critical print size, and acuity reserve of children with IN were tightly related to changes in their uncrowded distance acuity and the changes in magnitude and extent of crowding. CONCLUSIONS: Our findings are the first to show that visual acuity is not the only factor that restricts reading in children with IN, but that crowding also limits their reading performance. By targeting both of these spatial bottlenecks in children with IN, our perceptual learning paradigms significantly improved their reading acuity and critical print size. This shows that perceptual learning can effectively transfer to reading.

Contains fulltext : 168040.pdf (Publisher’s version ) (Open Access) PURPOSE: To evaluate whether computerized training with a crowded or uncrowded letter-discrimination task reduces visual impairment (VI) in 6- to 11-year-old children with infantile nystagmus (IN) who suffer from increased foveal crowding, reduced visual acuity, and reduced stereopsis. METHODS: Thirty-six children with IN were included. Eighteen had idiopathic IN and 18 had oculocutaneous albinism. These children were divided in two training groups matched on age and diagnosis: a crowded training group (n = 18) and an uncrowded training group (n = 18). Training occurred two times per week during 5 weeks (3500 trials per training). Eleven age-matched children with normal vision were included to assess baseline differences in task performance and test-retest learning. Main outcome measures were task-specific performance, distance and near visual acuity (DVA and NVA), intensity and extent of (foveal) crowding at 5 m and 40 cm, and stereopsis. RESULTS: Training resulted in task-specific improvements. Both training groups also showed uncrowded and crowded DVA improvements (0.10 +/- 0.02 and 0.11 +/- 0.02 logMAR) and improved stereopsis (670 +/- 249''). Crowded NVA improved only in the crowded training group (0.15 +/- 0.02 logMAR), which was also the only group showing a reduction in near crowding intensity (0.08 +/- 0.03 logMAR). Effects were not due to test-retest learning. CONCLUSIONS: Perceptual learning with or without distractors reduces the extent of crowding and improves visual acuity in children with IN. Training with distractors improves near vision more than training with single optotypes. Perceptual learning also transfers to DVA and NVA under uncrowded and crowded conditions and even stereopsis. Learning curves indicated that improvements may be larger after longer training.

Item does not contain fulltext Cerebral visual impairment (CVI) is a major cause of low vision in children due to impairment in projection and/or interpretation of the visual input in the brain. Although acquired causes for CVI are well known, genetic causes underlying CVI are largely unidentified. DNAs of 25 patients with CVI and intellectual disability, but without acquired (eg, perinatal) damage, were investigated by whole-exome sequencing. The data were analyzed for de novo, autosomal-recessive, and X-linked variants, and subsequently classified into known, candidate, or unlikely to be associated with CVI. This classification was based on the Online Mendelian Inheritance in Man database, literature reports, variant characteristics, and functional relevance of the gene. After classification, variants in four genes known to be associated with CVI (AHDC1, NGLY1, NR2F1, PGAP1) in 5 patients (20%) were identified, establishing a conclusive genetic diagnosis for CVI. In addition, in 11 patients (44%) with CVI, variants in one or more candidate genes were identified (ACP6, AMOT, ARHGEF10L, ATP6V1A, DCAF6, DLG4, GABRB2, GRIN1, GRIN2B, KCNQ3, KCTD19, RERE, SLC1A1, SLC25A16, SLC35A2, SOX5, UFSP2, UHMK1, ZFP30). Our findings show that diverse genetic causes underlie CVI, some of which will provide insight into the biology underlying this disease process.

Contains fulltext : 168206.pdf (Publisher’s version ) (Open Access) BACKGROUND: The inclusion for rehabilitation of visually impaired children is partly based on the measurement of near vision, but guidelines for near visual acuity assessment are currently lacking. The twofold purpose of this systematic review was to: (i) provide an overview of the impact of the chart design on near visual acuity measured, and (ii) determine the method of choice for near vision assessments in children of different developmental ages. METHODS: A literature search was conducted by using the following electronic databases: PubMed, Cochrane Library, and EMBASE. The last search was run on March 26th 2016. Additional studies were identified by contacting experts and searching for relevant articles in reference lists of included studies. Search terms were: vision test(s), vision assessment(s), visual acuity, chart(s) and near. RESULTS: For children aged 0-3 years the golden standard is still the preferential looking procedure. Norms are available for this procedure for 6-36 month old children. For 4-7 year olds, we recommend using the LEA symbols, because these symbols have been properly validated and can be used in preliterate children. Responses can be verbal or by matching the target symbol. In children aged 8-13 years, the recommended method is the ETDRS letter chart, because letter acuity is more predictive for functional vision and reading than symbol acuity. In 8-13 year olds, letter acuity is 0.1-0.2 logMAR poorer than symbol acuity. CONCLUSIONS: Chart design, viewing distance, and threshold choice have a serious impact on near visual acuity measurements. Near visual acuity measured with symbols is lower than near visual acuity measured with gratings, and near visual acuity measured with letters is lower than near visual acuity measured with symbols. Viewing distance, chart used, and letter spacing should be adapted to the child's development and reported in order to allow comparisons between measurements.

Purpose We measured visual acuity and visual discrimination speed simultaneously in children with visual impairments to determine whether they are slower than children with normal vision. Methods Five- to twelve-year-old children with visual impairments due to ocular dysfunction (VIo; n = 30) or cerebral visual impairment (CVI; n = 17) performed a speed-acuity test in which they indicated the orientation of Landolt-C symbols as quickly and accurately as possible. The reaction times for symbols ranging between -0.3 and 1.2 logMAR relative to acuity threshold were compared with normative data. To test whether children were already slow in merely detecting symbols, we also compared their reaction times on a simple visual detection task (VDT) to normative data. An auditory detection task (ADT) was used to probe for other, more general deficits. Results Of the children with visual impairments, 88% had abnormally long reaction times in the speed-acuity test. This deficit was partly explained by their reduced acuity, but 40% still needed more time to discriminate acuity-matched optotypes. Children responded late in the VDT too, especially those with CVI, but this impairment could not fully account for their slow symbol discrimination. In children with CVI, reaction times in the ADT were affected as much as those in the VDT, suggesting more general sensorimotor problems in CVI. Conclusions The speed-acuity test offers additional insight in visual impairment. Children with VIo and CVI are abnormally slow in discerning foveal details. Magnification of materials is often insufficient to compensate for this deficit, partly because stimulus detection is already hampered.

Contains fulltext : 181708.pdf (Publisher’s version ) (Open Access) The useful-field-of-view (UFOV) test measures the amount of information someone can extract from a visual scene in one glance. Its scores show relatively strong relationships with everyday activities. The UFOV test consists of three computer tests, suggested to measure processing speed and central vision, divided attention, and selective attention. However, other functions seem to be involved as well. In order to investigate the contribution of these suggested and other perceptual and cognitive functions, we performed a meta-analysis of 116 Pearson's correlation coefficients between UFOV scores and other test scores reported in 18 peer-reviewed articles. We divided these correlations into nine domains: attention, executive functioning, general cognition, memory, spatial ability, visual closure, contrast sensitivity, visual processing speed, and visual acuity. A multivariate mixed-effects model analysis revealed that each domain correlated significantly with each of the UFOV subtest scores. These correlations were stronger for Subtests 2 and 3 than for Subtest 1. Furthermore, some domains were more strongly correlated to the UFOV than others across subtests. We did not find interaction effects between subtest and domain, indicating that none of the UFOV subtests is more selectively sensitive to a particular domain than the others. Thus, none of the three UFOV subtests seem to measure one clear construct. Instead, a range of visual and cognitive functions is involved. Perhaps this is the reason for the UFOV's high ecological validity, as it involves many functions at once, making it harder to compensate if one of them fails.

Item does not contain fulltext Optic nerve atrophy and hypoplasia can be primary disorders or can result from trans-synaptic degeneration arising from cerebral visual impairment (CVI). Here we report six individuals with CVI and/or optic nerve abnormalities, born after an uneventful pregnancy and delivery, who have either de novo heterozygous missense mutations in NR2F1, also known as COUP-TFI, or deletions encompassing NR2F1. All affected individuals show mild to moderate intellectual impairment. NR2F1 encodes a nuclear receptor protein that regulates transcription. A reporter assay showed that missense mutations in the zinc-finger DNA-binding domain and the putative ligand-binding domain decrease NR2F1 transcriptional activity. These findings indicate that NR2F1 plays an important role in the neurodevelopment of the visual system and that its disruption can lead to optic atrophy with intellectual disability.

Contains fulltext : 123733.pdf (Publisher’s version ) (Open Access) This study investigates the influence of oculomotor control, crowding, and attentional factors on visual search in children with normal vision ([NV], n = 11), children with visual impairment without nystagmus ([VI−nys], n = 11), and children with VI with accompanying nystagmus ([VI+nys], n = 26). Exclusion criteria for children with VI were: multiple impairments and visual acuity poorer than 20/400 or better than 20/50. Three search conditions were presented: a row with homogeneous distractors, a matrix with homogeneous distractors, and a matrix with heterogeneous distractors. Element spacing was manipulated in 5 steps from 2 to 32 minutes of arc. Symbols were sized 2 times the threshold acuity to guarantee visibility for the VI groups. During simple row and matrix search with homogeneous distractors children in the VI+nys group were less accurate than children with NV at smaller spacings. Group differences were even more pronounced during matrix search with heterogeneous distractors. Search times were longer in children with VI compared to children with NV. The more extended impairments during serial search reveal greater dependence on oculomotor control during serial compared to parallel search. 10 p.

Contains fulltext : 89704.pdf (Publisher’s version ) (Closed access) Familial exudative vitreoretinopathy (FEVR) is a genetically heterogeneous retinal disorder characterized by abnormal vascularisation of the peripheral retina, often accompanied by retinal detachment. To date, mutations in three genes (FZD4, LRP5, and NDP) have been shown to be causative for FEVR. In two large Dutch pedigrees segregating autosomal-dominant FEVR, genome-wide SNP analysis identified an FEVR locus of approximately 40 Mb on chromosome 7. Microsatellite marker analysis suggested similar at risk haplotypes in patients of both families. To identify the causative gene, we applied next-generation sequencing in the proband of one of the families, by analyzing all exons and intron-exon boundaries of 338 genes, in addition to microRNAs, noncoding RNAs, and other highly conserved genomic regions in the 40 Mb linkage interval. After detailed bioinformatic analysis of the sequence data, prioritization of all detected sequence variants led to three candidates to be considered as the causative genetic defect in this family. One of these variants was an alanine-to-proline substitution in the transmembrane 4 superfamily member 12 protein, encoded by TSPAN12. This protein has very recently been implicated in regulating the development of retinal vasculature, together with the proteins encoded by FZD4, LRP5, and NDP. Sequence analysis of TSPAN12 revealed two mutations segregating in five of 11 FEVR families, indicating that mutations in TSPAN12 are a relatively frequent cause of FEVR. Furthermore, we demonstrate the power of targeted next-generation sequencing technology to identify disease genes in linkage intervals.

Contains fulltext : 135955.pdf (Publisher’s version ) (Open Access) BACKGROUND: To gain more insight into genetic causes of cerebral visual impairment (CVI) in children and to compare ophthalmological findings between genetic and acquired forms of CVI. METHODS: The clinical data of 309 individuals (mainly children) with CVI, and a visual acuity