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A study reports that mutations in the small GTPase gene RAB39B are responsible for X-linked Human Mental Retardation (HMR) associated with autism, epilepsy, and macrocephaly. Analyses demonstrate that RAB39B, a novel GTPase of the RAB family, is a neuronal-specific protein required for synapse formation and maintenance, and its downregulation due to mutations impairs the development of neurons and human intellectual abilities.

We performed a multilevel, multinational analysis of the 2014 European Social Survey dataset (N = 33,597, nested in 19 countries) to study how individual conservative values and cultural embeddedness moderate the link between contact with immigrants and the attitudes toward them. A combination of frequency and positivity of contact with immigrants showed a negative association with ethnic prejudice while, conversely, participants' conservative basic values were directly and positively associated with prejudice. National cultural embeddedness was not associated with the dependent variable. Neither individual conservative values nor cultural embeddedness moderated the association between contact and prejudice. Strengths, limitations, implications and future directions of this study are discussed. [ABSTRACT FROM AUTHOR]

In this study we adopted an agentic perspective and used self-determination theory to analyze the role of political interest in youth's sociopolitical development. Inspired by this theoretical framework, we identified indicators of the needs for autonomy, relatedness, and competence within the political sphere. We followed two age cohorts (Swedish 13- and 16-year-olds) over one year, with a total of 1992 adolescents, who are at a crucial age for sociopolitical development. Results from autoregressive structural cross-lagged models indicated that political interest predicted significant increases in autonomy, relatedness, and competence over one year, but these psychological needs did not predict a change in political interest over the same time period. The findings speak in favor of an agentic perspective, suggesting that political interest can serve as a basis for youth's political development. [ABSTRACT FROM AUTHOR]

Discussing politics in everyday life is quite common but it is not clear how talking politics should prompt the desire to become politically active. We compared two ideas: information gain, i.e., political talk translates into action when people receive information about activities and organizations; and social influence, i.e., political talk translates into action when people perceive their friends as politically active. Our main goal was to address the role played by two personality traits – Openness to Experience and Agreeableness – within these processes. Adopting a longitudinal design ( N = 895, sample of youths surveyed twice), we found that political talk promotes political participation over time when people perceive their discussion partners as politically active and that this effect is especially pronounced for agreeable people. Findings from this study provided support to the idea that political talk translates into political action under the condition of social influence and for people who are particularly susceptible to social conformity. [ABSTRACT FROM AUTHOR]

Purpose We investigated drugs most often used to treat epilepsy in Rett Syndrome and their efficacy in a large cohort of Italian patients. Methods This is a multi-centre retrospective study. Data of 165 Rett subjects were collected from the patients' files, and hospital charts. The efficacy of antiepileptic drugs (AEDs) was classified as follows: not effective; decrease in seizure frequency ≥50% for at least 6 months; seizure-free for at least 2 years. Phenotypic and genetic categorization of patients was performed and it was considered in AEDs efficacy evaluation. Results There were 130 epileptic patients.Sodium valproate (VPA) was the most commonly administered AED (44.3%) at seizure onset, followed by Carbamazepine (CBZ) (25.4%) and Phenobarbital (PB) (13%). Monotherapy was the first treatment option in most patients. VPA and CBZ proved to be equally effective in Rett patients who presented seizures within the typical age range (4–5 years), while Lamotrigine (LTG) was effective for patients in whom epilepsy started later. Overall, the frequency of side effects was low and the most often observed ones were restlessness and somnolence. Conclusion Our study suggests that LTG, VPA and CBZ can be used as drugs of first choice in Rett Syndrome. The association of four drugs should be avoided since it did not result in any significant clinical improvement. [ABSTRACT FROM AUTHOR]

Objective: To compare tumor risk in the 4 Beckwith-Wiedemann syndrome (BWS) molecular subgroups: Imprinting Control Region 1 Gain of Methylation (ICR1-GoM), Imprinting Control Region 2 Loss of Methylation (ICR2-LoM), Chromosome 11p15 Paternal Uniparental Disomy (UPD), and Cyclin-Dependent Kinase Inhibitor 1C gene (CDKN1C) mutation.Study Design: Studies on BWS and tumor development published between 2000 and 2015 providing (epi)genotype-cancer correlations with histotype data were reviewed and meta-analysed with cancer histotypes as measured outcome and (epi)genotype as exposure.Results: A total of 1370 patients with BWS were included: 102 developed neoplasms (7.4%). Tumor prevalence was 2.5% in ICR2-LoM, 13.8% in UPD, 22.8% in ICR1-GoM, and 8.6% in patients with CDKN1C mutations. Cancer ORs were 12.8 in ICR1-GoM, 6.5 in UPD, and 2.9 in patients with CDKN1C mutations compared with patients with ICR2-LoM. Wilms tumor was associated with ICR1-GoM (OR 68.3) and UPD (OR 13.2). UPD also was associated with hepatoblastoma (OR 5.2) and adrenal carcinoma (OR 7.0), and CDKN1C mutations with neuroblastic tumors (OR 7.2).Conclusion: Cancer screening in BWS could be differentiated on the basis of (epi)genotype and target specific histotypes. Patients with ICR1-GoM and UPD should undergo renal ultrasonography scanning, given their risk of Wilms tumor. Alpha feto protein monitoring for heptaoblastoma is suggested in patients with UPD. Adrenal carcinoma may deserve screening in patients with UPD. Patients with CDKN1C mutations may deserve neuroblastoma screening based on urinary markers and ultrasonography scanning. Finally, screening appears questionable in cases of ICR2-LoM, given low tumor risk. [ABSTRACT FROM AUTHOR]

The literature shows that exposure to societal threat stemming from criminality can elicit an increase in right-wing authoritarianism (RWA) via the mediation of the loss of perceived control. In this study, we investigated whether the perception of meaning can act as a buffering factor for such process, performing an experiment with 316 Italian university students (67.8% women; mean age = 25.81, SD = 9.18). A moderated mediation model showed that the loss of perceived control mediated the relation between societal threat stemming from criminality and RWA, but that the second link was significant only among people low in meaning. Limitations, implications and possible developments of this research are discussed. [ABSTRACT FROM AUTHOR]

Mutations in MECP2 gene cause Rett syndrome (RTT), a neurodevelopmental disorder affecting around 1 in 10,000 female births. The clinical picture of RTT appears quite heterogeneous for each single feature. Mutations in MECP2 gene have been associated with the onset of RTT. The most known gene function consists of transcriptional repression of specific target genes, mainly by the binding of its methyl binding domain (MBD) to methylated CpG nucleotides and recruiting co-repressors and histone deacetylase binding to DNA by its transcription repressor domain (TRD). This study aimed at evaluating a cohort of 114 Rett syndrome (RTT) patients with a detailed scale measuring the different kinds of impairments produced by the syndrome. The sample included relatively large subsets of the most frequent mutations, so that genotype–phenotype correlations could be tested. Results revealed that frequent missense mutations showed a specific profile in different areas of impairment. The R306C mutation, considered as producing mild impairment, was associated to a moderate phenotype in which behavioural characteristics were mainly affected. A notable difference emerged by comparing mutations truncating the protein before and after the nuclear localization signal; such a difference concerned prevalently the motor-functional and autonomy skills of the patients, affecting the management of everyday activities. [ABSTRACT FROM AUTHOR]

We tested the hypothesis that parental support for autonomy moderates the effects of societal threat to safety on the development of right-wing authoritarianism (RWA). In a quasi-experimental study performed on 241 Italian university students, societal threat to safety fostered RWA only among participants who reported low levels of parental support for autonomy. [ABSTRACT FROM AUTHOR]

Abstract: Cornelia de Lange syndrome (CdLS, OMIM #122470, #300590, #610759, #614701, #300882) is a rare neurodevelopmental syndrome characterized by growth retardation, intellectual disability, dysmorphic facial features, multisystem malformations, and limb reduction defects. Wide variability of phenotypes is common among CdLS patients. Mutations in genes encoding either regulators (NIPBL, HDAC8) or subunits (SMC1A, SMC3, RAD21) of the cohesin complex, are altogether found in approximately 65% of CdLS patients. We describe a CdLS patient with classic severe phenotype who was found negative to mutations in the NIPBL and SMC1A genes by DHPLC and direct sequencing. MLPA analysis performed to disclose potential intragenic NIPBL deletions/duplications, suggested a partial deletion which was confirmed by FISH with a BAC clone encompassing the NIPBL region that highlighted asymmetric signals in a fraction of cells (72%). The occurrence of a genomic deletion in mosaic condition was validated by array-CGH analysis. Long-range PCR and sequencing of the junction fragment mapped the telomeric and the centromeric breakpoint within NIPBL IVS1 and IVS32, respectively. Both deletion breakpoints were embedded in a microsatellite region that might be the motif directly mediating this large deletion by an intrachromatid recombination mechanism. Consistent with the molecular analyses, the patient displayed a severe phenotype that was characterized by drastic CdLS clinical signs including premature death. This case provides a second example of mosaicism in CdLS. Despite mitigated by mosaicism, the large intragenic deletion identified in the present case was poorly tolerated due to the high mosaicism level. Based on these data, overlooked cases of mosaicism may lead to underestimated mutation rates of known genes and may also contribute to the clinical heterogeneity of CdLS. [Copyright &y& Elsevier]

Abstract: We describe a 7-year-old boy with a complex rearrangement involving the whole short arm of chromosome 9 defined by means of molecular cytogenetic techniques. The rearrangement is characterized by a 18.3Mb terminal deletion associated with the inverted duplication of the adjacent 21,5Mb region. The patient shows developmental delay, psychomotor retardation, hypotonia. Other typical features of 9p deletion (genital disorders, midface hypoplasia, long philtrum) and of the 9p duplication (brachycephaly, down slanting palpebral fissures and bulbous nasal tip) are present. Interestingly, he does not show trigonocephaly that is the most prominent dysmorphism associated with the deletion of the short arm of chromosome 9. Patient''s phenotype and the underlying flanking opposite 9p imbalances are compared with that of reported patients and the proposed critical regions for 9p deletion and 9p duplication syndromes. [Copyright &y& Elsevier]

Abstract: We identified a 495 Kb interstitial deletion of chromosome Xp22.2, centered on the AP1S2 gene, by means of oligonucleotide array comparative genomic hybridisation (array-CGH) in a child with marked hypotonia in the first months of life, psychomotor retardation, severely delayed walking and speech development, and unspecific dysmorphic facial features. The deletion was inherited from the healthy mother. Point mutations of the AP1S2 gene have been identified in patients with X-linked mental retardation (XLMR). The clinical features of our patient are quite similar to those reported in male patients carrying point mutations, thus suggesting that point mutations and deletions of the AP1S2 gene lead to a recognisable XLMR phenotype in males. [Copyright &y& Elsevier]

Abstract: The aetiology of autism is still largely unknown despite analyses from family and twin studies demonstrating substantial genetic role in the aetiology of the disorder. Data from linkage studies and analyses of chromosomal abnormalities identified 15q11-q13 as a region of particular aetiopathogenesis interest. We screened a set of markers spanning two known imprinted, maternally expressed genes, UBE3A and ATP10A, harboured in this candidate region. We replicated evidence of linkage disequilibrium (LD) at marker D15S122, located at the 5'' end of UBE3A and originally reported by Nurmi et al. (2001). The potential role of UBE3A in our family-based association study is further supported by the association of two haplotypes that include one of the alleles of D15S122 and by the transmission disequilibrium test (TDT) evidence of the same allele in a parent of origin effect analysis. In a secondary analysis, we provided the first evidence of a significant association between first word delay and psychomotor regression with the 15q11-q13 region. Our data support a potential role of UBE3A in the complex pathogenic mechanisms of autism. [Copyright &y& Elsevier]

Cornelia de Lange syndrome is a rare autosomal dominant or X-linked developmental disorder characterized by characteristic facial dysmorphism, intellectual disability, growth retardation, upper limb and multiorgan anomalies. Causative mutations have been identified in five genes coding for the cohesion complex structure components or regulatory elements. Among them, RAD21 is associated with a milder phenotype. Very few RAD21 intragenic mutations have been identified so far. Thus, any new patient is a valuable tool to delineate the associated phenotype. We discuss a new patient with RAD21 confirmed molecular diagnosis and compare his clinical features to those of previously described patients carrying different RAD21 intragenic mutations. [ABSTRACT FROM AUTHOR]