A novel WNT10A mutation causes non-syndromic hypodontia in an Egyptian family

Objective

Tooth agenesis is the most common dental anomaly, whose aetiology still remains to be fully elucidated. The aim of this study was to investigate the genetic cause of non-syndromic hypodontia with clinical variability in an Egyptian family.

Design

The entire coding regions including exon-intron boundaries of the MSX1, PAX9 and WNT10A genes were investigated by direct sequencing in all affected family members.

Results

Novel heterozygous mutation inherited in an autosomal dominant manner was identified in the WNT10A gene. This 21-bp deletion combined with 1-bp insertion, c.-14_7delinsC, eliminates the translation initiation codon leading to either no protein production or translation of alternative open reading frames. None of the control subjects (400 chromosomes) were carriers of this novel WNT10A mutation. No pathogenic mutations were found in the MSX1 and PAX9 genes.

Conclusions

The novel c.-14_7delinsC mutation might be the etiological variant of the WNT10A gene responsible for the permanent tooth agenesis in the Egyptian family. WNT10A is a major candidate gene for non-syndromic hypodontia.     

Computerized assessment of cognition in schizophrenia: promises and pitfalls of CANTAB.

OBJECTIVE: Over the last decade, the Cambridge Neuropsychological Test Automated Battery (CANTAB), which comprises visuo-spatial tasks, has been utilized in cognitive studies of schizophrenia. A clear approach concerning the usage of CANTAB for the appraisal of neurocognitive dysfunction in schizophrenia is currently lacking. METHOD: In this paper, we have first reviewed the overall applications of CANTAB and then evaluated methodological strengths and weaknesses of CANTAB as a neurocognitive battery for schizophrenia. We carried out a systematic search and assessment of studies where CANTAB was utilized to measure cognitive function in schizophrenia. We have also attempted to quantify the available data and perform a meta-analysis, but this approach turned out to be still premature. RESULTS: CANTAB has enabled researchers to highlight significant deficits affecting broad cognitive domains in schizophrenia, such as working memory, decision-making, attention, executive functions and visual memory. So far, the most consistent deficit observed with CANTAB testing has been attentional set-shifting, suggestive of fronto-striatal dysfunctions. In addition, preliminary evidence points towards the potential use of CANTAB to identify cognitive predictors of psychosocial functioning, to describe the relationships between symptoms and cognition, and to measure the impact of pharmacological agents on cognitive functioning. CONCLUSION: CANTAB has been used successfully to highlight the range of visuo-spatial cognitive deficits in schizophrenia, producing similar results to those obtained with some traditional neuropsychological tests. Further studies validating the use of CANTAB following the standard set by Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) are warranted.     

Repetition suppression of ventromedial prefrontal activity during judgments of self and others

One useful strategy for inferring others' mental states (i.e., mentalizing) may be to use one's own thoughts, feelings, and desires as a proxy for those of other people. Such self-referential accounts of social cognition are supported by recent neuroimaging observations that a single brain region, ventromedial prefrontal cortex (vMPFC), is engaged both by tasks that require introspections about self and by tasks that require inferences about the minds of others perceived to be similar to self. To test whether people automatically refer to their own mental states when considering those of a similar other, we examined repetition-related suppression of vMPFC response during self-reflections that followed either an initial reflection about self or a judgment of another person. Consistent with the hypothesis that perceivers spontaneously engage in self-referential processing when mentalizing about particular individuals, vMPFC response was suppressed when self-reflections followed either an initial reflection about self or a judgment of a similar, but not a dissimilar, other. These results suggest that thinking about the mind of another person may rely importantly on reference to one's own mental characteristics.     

A country divided? Regional variation in mortality in Ukraine

Objectives

We set out to identify the contribution of various causes of death to regional differences in life expectancy in Ukraine.

Methods

Mortality data by oblast (province) were obtained from the State Statistical Committee of Ukraine. The contribution of various causes of death to differences in life expectancy between East, West and South Ukraine was estimated using decomposition.

Results

In 2008, life expectancy for men in South (61.8 years) and East Ukraine (61.2 years) was lower than for men in West Ukraine (64.0 years). A similar pattern was observed among women. This was mostly due to deaths from infectious disease and external causes among young adults, and cardio- and cerebro-vascular deaths among older adults. Deaths from TB among young adults contribute most to differences in life expectancy.

Conclusions

Deaths due to infectious disease, especially TB, play an important role in the gap in life expectancy between regions in Ukraine. These deaths are entirely preventable—further research is needed to identify what has ‘protected’ individuals in Western Ukraine from the burden of deaths experienced by their Southern and Eastern counterparts.     

Atypical processing of auditory temporal complexity in autistics

Autistics exhibit a contrasting combination of auditory behavior, with enhanced pitch processing abilities often coexisting with reduced orienting towards complex speech sounds. Based on an analogous dissociation observed in vision, we expected that autistics’ auditory behavior with respect to complex sound processing may result from atypical activity in non-primary auditory cortex. We employed fMRI to explore the neural basis of complex non-social sound processing in 15 autistic and 13 non-autistics, using a factorial design in which auditory stimuli varied in spectral and temporal complexity. Spectral complexity was modulated by varying the harmonic content, whereas temporal complexity was modulated by varying frequency modulation depth. The detection task was performed similarly by autistics and non-autistics. In both groups, increasing spectral or temporal complexity was associated with activity increases in primary (Heschl's gyrus) and non-primary (anterolateral and posterior superior temporal gyrus) auditory cortex Activity was right-lateralized for spectral and left-lateralized for temporal complexity. Increasing temporal complexity was associated with greater activity in anterolateral superior temporal gyrus in non-autistics and greater effects in Heschl's gyrus in autistics. While we observed similar hierarchical functional organization for auditory processing in both groups, autistics exhibited diminished activity in non-primary auditory cortex and increased activity in primary auditory cortex in response to the presentation of temporally, but not of spectrally complex sounds. Greater temporal complexity effects in regions sensitive to acoustic features and reduced temporal complexity effects in regions sensitive to more abstract sound features could represent a greater focus towards perceptual aspects of speech sounds in autism.