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Objective: Data on the value of exome sequencing in fetuses with no structural anomalies are limited, especially in the early stages of pregnancy and in low risk pregnancies. We investigated the yield of targeted clinical prenatal trio exome sequencing (pES) in pregnancies with and without fetal structural anomalies. Methods: We performed pES in 353 pregnancies: Group 1 included 143 pregnancies with high clinical suspicion for a genetic disease: pregnancies with increased nuchal translucency, ultrasound structural defects, intrauterine growth restriction, polyhydramnios, or effusion/nuchal edema. Group 2 included 210 pregnancies with no notable abnormal fetal ultrasound findings. 2a. Low risk pregnancies with minor ultrasound findings, referred to the geneticist due to mildly increased risk for genetic disease (50); and 2b. Normal pregnancy surveillance (160). Results: Overall, 26 (7.36%) fetal analyses had pathogenic (P)/likely pathogenic (LP) variants. In group 1, 20/143 (13.99%) cases had P/LP variants. In group 2, 6/210 (2.86%) cases were found to have P/LP variants [5/50 in (2a) and 1/160 in (2b)]. Conclusion: These results show a high rate of abnormal findings on pES even in apparently normal pregnancies. Key points: What's already known about this topic? Previous studies demonstrated that exome sequencing contribute a substantial diagnostic information in pregnancies when the fetus present major structural defects and anomalies What does this study add? This study centers around the inclusion of low risk pregnancies; those with minor ultrasound findings and those with normal pregnancy surveillance. Our findings show that exome sequencing among low risk pregnancies contributed significant and important critical diagnostic information [ABSTRACT FROM AUTHOR]

Key points: What's already known?Variants in CCND2 gene are known to cause syndromic macrocephaly. Recently inverse growth proximal variants were described in five individuals with microcephaly. What does this study add?CCND2 loss of function distal variants can cause fetal microcephaly. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a common heritable neurodevelopmental disorder, which is characterized by communication and social deficits that reduce the reproductive fitness of individuals with the disorder. Here, we studied the genomic characteristics of 651 ASD genes in a whole-exome sequencing dataset, to search for traces of the evolutionary forces that helped maintain ASD in the human population. We show that ASD genes are ~65 longer and ~20 % less variable than non-ASD genes. The mutational shortage in ASD genes was particularly eminent when considering only deleterious genetic variations, which is a hallmark of negative selection. We further show that these genomic characteristics are unique to ASD genes, as compared with brain-specific genes or with genes of other diseases. Our findings suggest that ASD genes have evolved under complex evolutionary forces, which have left a unique signature that can be used to identify new candidate ASD genes. [ABSTRACT FROM AUTHOR]

The ‘certainty effect’ is a notable violation of expected utility theory by decision makers. It shows that people’s tendency to select the safer of two prospects increases when this prospect provides a good outcome with certainty (for example, people prefer a monetary gain of 3 with certainty over 4 with a probability of 0.8, but do not prefer 3 with a probability of 0.25 over 4 with a probability of 0.2). Subsequent work on experience-based decision making in rats extended the certainty effect to other animals, suggesting its generality across different species and different decision-making mechanisms. However, an attempt to replicate this study with human subjects showed a surprising ‘reversed certainty effect’, namely, the tendency to prefer the safer option decreases when this prospect is associated with certainty (and people now prefer 4 with a probability of 0.8 over 3 with certainty). Here we show that these conflicting results can be explained by perceptual noise and that the certainty effect can be restored experimentally by reducing perceptual accuracy. Using complementary experiments in humans and honeybees (Apis mellifera), we show that by manipulating perceptual accuracy in experience-based tasks, both the certainty and the reversed certainty effects can be exhibited by humans and other animals: the certainty effect emerges when it is difficult to discriminate between the different rewards, whereas the reversed certainty effect emerges when discrimination is easy. Our results fit a simple process-based model of matching behaviour, capable of explaining the certainty effect in humans and other animals that make repeated decisions based on experience. This mechanism should probably be distinguished from those involved in the original certainty effect that was exhibited by human subjects in single description-based problems. [ABSTRACT FROM AUTHOR]