Deaf individuals who learned a spoken language with the aid of a cochlear implant (CI) often experience difficulties with reading. In the present study, we investigate this issue by assessing the ...impact of lexical and orthographic predictors on visual word recognition in early and late deaf CI-users. Early deaf CI-users were comparable to age-matched hearing controls, for both response accuracy and latencies, whereas late deaf CI-users were slower albeit similarly accurate with respect to age-matched controls. Analyses of the impact of lexical and orthographic predictors, however, revealed that early deaf-CI users were slower than controls in recognising low frequency words and words with high proportion of consonants. In conclusion, early deaf individuals who developed their language using a CI show qualitative differences in visual word processing, above and beyond the overall performance. This suggests that typical overall performance may emerge also in the context of atypical lexical and word form representations.
Loss-of-function variants in CHAMP1 were recently described as cause of a neurodevelopmental disorder characterized by intellectual disability (ID), autism, and distinctive facial characteristics. By ...exome sequencing (ES), we identified a truncating variant in CHAMP1, c.1858A > T (p.Lys620*), in a patient who exhibited a similar phenotype of severe ID and dysmorphisms. Whether haploinsufficiency or a dominant negative effect is the underlying pathomechanism in these cases is a question that still needs to be addressed. By array-CGH, we detected a 194 kb deletion in 13q34 encompassing CHAMP1, CDC16 and UPF3, in another patient who presented with borderline neurodevelopmental impairment and with no dysmorphisms. In a further patient suffering from early onset refractory seizures, we detected by ES a missense variant in CHAMP1, c.67 G > A (p.Gly23Ser). Genomic abnormalities were all de novo in our patients. We reviewed the clinical and the genetic data of patients reported in the literature with: loss-of-function variants in CHAMP1 (total 40); chromosome 13q34 deletions ranging from 1.1 to 4 Mb (total 7) and of the unique patient with a missense variant. We could infer that loss-of-function variants in CHAMP1 cause a homogeneous phenotype with severe ID, autism spectrum disorders (ASD) and highly distinctive facial characteristics through a dominant negative effect. CHAMP1 haploinsufficiency results in borderline ID with negligible consequences on the quality of life. Missense variants give rise to a severe epileptic encephalopathy through gain-of-function mechanism, most likely. We tentatively define for the first time distinct categories among the CHAMP1-related disorder on the basis of pathomechanisms.
One of the main factors influencing the clinical utility of genetic tests for cancer predisposition is the ability to provide actionable classifications (ie pathogenic or benign). However, a large ...fraction of the variants identified in cancer predisposing genes (CPGs) are of uncertain significance (VUS), and cannot be used for clinical purposes either to identify individuals at risk or to drive treatment.
Here we analyze the current status of VUS identification in a subset of 24 CPGs included by the American College of Medical Genetics/Association for Molecular Pathology in the list of genes that should be considered for the return of incidental findings. To this purpose we retrieved published literature using different search strings according to the frequency of the condition and we extracted corresponding data from ClinVar.
The total number of VUS has not decreased with time, due to widespread multigene panel testing, and the relative yield of VUS compared to pathogenic variants is higher in more recent studies, which tend to involve series not selected for the presence of specific high risk criteria. In addition, only few studies adopt gene specific interpretation criteria when these are available.
Despite the large yield of VUS associated with multigene testing, the data obtained from such studies can be very useful for variant classification, especially for those variants that are more likely to be benign, since these are expected to be detected more frequently in a population that does not show gene specific manifestations. In addition, wider use of gene specific interpretation criteria should be promoted in order to optimize the interpretation process.
Spermatogenesis-associated 5 like 1 (SPATA5L1) represents an orphan gene encoding a protein of unknown function. We report 28 bi-allelic variants in SPATA5L1 associated with sensorineural hearing ...loss in 47 individuals from 28 (26 unrelated) families. In addition, 25/47 affected individuals (53%) presented with microcephaly, developmental delay/intellectual disability, cerebral palsy, and/or epilepsy. Modeling indicated damaging effect of variants on the protein, largely via destabilizing effects on protein domains. Brain imaging revealed diminished cerebral volume, thin corpus callosum, and periventricular leukomalacia, and quantitative volumetry demonstrated significantly diminished white matter volumes in several individuals. Immunofluorescent imaging in rat hippocampal neurons revealed localization of Spata5l1 in neuronal and glial cell nuclei and more prominent expression in neurons. In the rodent inner ear, Spata5l1 is expressed in the neurosensory hair cells and inner ear supporting cells. Transcriptomic analysis performed with fibroblasts from affected individuals was able to distinguish affected from controls by principal components. Analysis of differentially expressed genes and networks suggested a role for SPATA5L1 in cell surface adhesion receptor function, intracellular focal adhesions, and DNA replication and mitosis. Collectively, our results indicate that bi-allelic SPATA5L1 variants lead to a human disease characterized by sensorineural hearing loss (SNHL) with or without a nonprogressive mixed neurodevelopmental phenotype.
► Autism and Asperger showed different conceptualization of emotional domain. ► Basic emotions (mainly anger, fear, happiness) were recognized by all sample. ► Surprise and disgust discriminated ...between the control and clinical sample. ► Contextual variable affected the subjects’ recognition process.
ASD subjects are described as showing particular difficulty in decoding emotional patterns. This paper explored linguistic and conceptual skills in response to emotional stimuli presented as emotional faces, scripts (pictures) and interactive situations (videos). Participants with autism, Asperger syndrome and control participants were shown facial, pictorial and video representation of six basic emotions (happiness, anger, fear, sadness, surprise, disgust). They were asked to identify the emotion and to individuate possible causes of the emotional state. A semantic analysis was applied to verbal reports, focusing on labeling and conceptualization. Log-linear analyses showed different representations across the participants as a function of emotion, pathology and presentation modality. Autistic participants were able to correctly decode primary emotions while showing difficulties with surprise. In contrast, Asperger participants performance was more similar to control subjects’. Finally, when situational correlates were provided, it was evident a “facilitation effect” for the representation of emotions.
This article presents the ENglish Reading Online (ENRO) project that offers data on English reading and listening comprehension from 7,338 university‐level advanced learners and native speakers of ...English representing 19 countries. The database also includes estimates of reading rate and seven component skills of English, including vocabulary, spelling, and grammar, as well as rich demographic and language background data. We first demonstrate high reliability for ENRO tests and their convergent validity with existing meta‐analyses. We then provide a bird's‐eye view of first (L1) and second (L2) language comparisons and examine the relative role of various predictors of reading and listening comprehension and reading speed. Across analyses, we found substantially more overlap than differences between L1 and L2 speakers, suggesting that English reading proficiency is best considered across a continuum of skill, ability, and experiences spanning L1 and L2 speakers alike. We end by providing pointers for how researchers can mine ENRO data for future studies.
A one‐page Accessible Summary of this article in non‐technical language is freely available in the Supporting Information online and at https://oasis‐database.org
Abstract
Research into second language (L2) reading is an exponentially growing field. Yet, it still has a relatively short supply of comparable, ecologically valid data from readers representing a ...variety of first languages (L1). This article addresses this need by presenting a new data resource called MECO L2 (Multilingual Eye Movements Corpus), a rich behavioral eye-tracking record of text reading in English as an L2 among 543 university student speakers of 12 different L1s. MECO L2 includes a test battery of component skills of reading and allows for a comparison of the participants’ reading performance in their L1 and L2. This data resource enables innovative large-scale cross-sample analyses of predictors of L2 reading fluency and comprehension. We first introduce the design and structure of the MECO L2 resource, along with reliability estimates and basic descriptive analyses. Then, we illustrate the utility of MECO L2 by quantifying contributions of four sources to variability in L2 reading proficiency proposed in prior literature: reading fluency and comprehension in L1, proficiency in L2 component skills of reading, extralinguistic factors, and the L1 of the readers. Major findings included (a) a fundamental contrast between the determinants of L2 reading fluency versus comprehension accuracy, and (b) high within-participant consistency in the real-time strategy of reading in L1 and L2. We conclude by reviewing the implications of these findings to theories of L2 acquisition and outline further directions in which the new data resource may support L2 reading research.
The present study explored the effect of different degrees of relevance in discourse comprehension by using ERPs analysis. A principle of pragmatic relevance is supposed to guide inferential ...mechanism underlying discourse processing. Discourse level comprehension needs a system of predictions about which information is more relevant in order to process the ongoing sentence meaning. This system should construct a specific mental model, where inferences related to the present sentence are stored and maintained. Three degrees of relevance of a new information (new sentence) with respect to an old information (target sentence) were manipulated: directly relevant; indirectly relevant; not relevant. Twenty-one subjects participated to the experiment and they were asked to try to comprehend a set of two paired sentences (old-new paired sentences) based on their conceptual relevance. Two negative deflections, peaking respectively at about 410 msec post-stimulus (N400), more right anterior-centrally distributed, and at about 550 msec (late negativity, LrN), more right central localized, were found. Repeated measures ANOVA found that the amplitude of both the N400 and LrNis modulated by the degree of relevance and by the strength of the underlying associations between the two sentences. Indirect relevance resulted in increased negativities in comparison with direct relevance. Contrarily, non-relevant condition did not produce an increasing in N400 and LrNamplitude. Unrelevance of the knowledge related to the actual mental model of sentences may induce a rapid and costless discarding of non pertinent information. The conclusive inference is that a subset of neural processes responding to degree of relevance of information is separable and cortically more frontally and centrally localized. Functional differences between N400 and LrN for relevance were discussed.
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