The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.
- MeSH
- abnormality očí enzymologie genetika MeSH
- alely MeSH
- dítě MeSH
- fenotyp MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- katarakta genetika MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- oči embryologie růst a vývoj MeSH
- rodokmen MeSH
- vývojové poruchy u dětí genetika MeSH
- zákal rohovky genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
The forkhead transcription factor FOXE3 is critical for vertebrate eye development. Recessive and dominant variants cause human ocular disease but the full range of phenotypes and mechanisms of action for the two classes of variants are unknown. We identified FOXE3 variants in individuals with congenital eye malformations and carried out in vitro functional analysis on selected alleles. Sixteen new recessive and dominant families, including six novel variants, were identified. Analysis of new and previously reported genetic and clinical data demonstrated a broad phenotypic range with an overlap between recessive and dominant disease. Most families with recessive alleles, composed of truncating and forkhead-domain missense variants, had severe corneal opacity (90%; sclerocornea in 47%), aphakia (83%) and microphthalmia (80%), but some had milder features including isolated cataract. The phenotype was most variable for recessive missense variants, suggesting that the functional consequences may be highly dependent on the type of amino acid substitution and its position. When assessed, aniridia or iris hypoplasia were noted in 89% and optic nerve anomalies in 60% of recessive cases, indicating that these defects are also common and may be underrecognized. In dominant pedigrees, caused by extension variants, normal eye size (96%), cataracts (99%) and variable anterior segment anomalies were seen in most, but some individuals had microphthalmia, aphakia or sclerocornea, more typical of recessive disease. Functional studies identified variable effects on the protein stability, DNA binding, nuclear localization and transcriptional activity for recessive FOXE3 variants, whereas dominant alleles showed severe impairment in all areas and dominant-negative characteristics.
- MeSH
- abnormality očí enzymologie genetika MeSH
- alely MeSH
- dítě MeSH
- fenotyp MeSH
- forkhead transkripční faktory genetika metabolismus MeSH
- katarakta genetika MeSH
- lidé MeSH
- mladiství MeSH
- mutace MeSH
- oči embryologie růst a vývoj MeSH
- rodokmen MeSH
- vývojové poruchy u dětí genetika MeSH
- zákal rohovky genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Analyses of user experience in the electronic entertainment industry currently rely on self-reporting methods, such as surveys, ratings, focus group interviews, etc. We argue that self-reporting alone carries inherent problems-mainly the misinterpretation and temporal delay during longer experiments-and therefore, should not be used as a sole metric. To tackle this problem, we propose the possibility of modeling consumer experience using psychophysiological measures and demonstrate how such models can be trained using machine learning methods. We use a machine learning approach to model user experience using real-time data produced by the autonomic nervous system and involuntary psychophysiological responses. Multiple psychophysiological measures, such as heart rate, electrodermal activity, and respiratory activity, have been used in combination with self-reporting to prepare training sets for machine learning algorithms. The training data was collected from 31 participants during hour-long experiment sessions, where they played multiple video-games. Afterwards, we trained and compared the results of four different machine learning models, out of which the best one produced ∼96% accuracy. The results suggest that psychophysiological measures can indeed be used to assess the enjoyment of digital entertainment consumers.
- MeSH
- algoritmy MeSH
- autonomní nervový systém fyziologie MeSH
- dospělí MeSH
- galvanická kožní odpověď fyziologie MeSH
- lidé MeSH
- mladý dospělý MeSH
- psychofyziologie metody MeSH
- srdeční frekvence fyziologie MeSH
- strojové učení MeSH
- videohry psychologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
