Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Niklas Luhmann - oder: Was ist ein 'differenztheoretischer' Ansatz?

UuStB Koeln=38*- 11L376 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Materialismo e primado do objeto em Adorno Materialism e priority of the object on Adorno

Este artigo investiga a "Tese" do primado do objeto na obra de Theodor W. Adorno, central ao seu materialismo não dogmático e relativamente pouco estudada. O primado do objeto será apresentado em seus elementos constitutivos, como crítica ao modo essencialmente idealista da dialética que perpassa o conjunto da obra de Adorno, em especial nos textos e discussões que precederam a publicação da Dialektik der Aufklãrung, para se explicitar no período de elaboração da Negative Dialektik. A "Tese" desenvolve momentos apresentados por Lukács, Benjamin e Horkheimer, particularmente quanto ao nexo entre razão e experiência e se fundamenta especialmente no trajeto Kant - Hegel, como crítica ao idealismo, incorporando de modo estruturante as perspectivas de Marx e de Nietzsche. Ao romper a pretensa "simetria" entre sujeito e objeto, a "Tese" do primado do objeto revela como é insustentável a alegação habermasiana do Discurso filosófico da modernidade segundo a qual Adorno e Horkheimer incidiriam num ceticismo total frente à razão e à sua totalização ideológica. Ao contrário: estes autores, ao articularem de um modo original substância material histórica e argumentação teórica, contribuíram de modo fundamental para examinar o problema da reificação mediante sua relação à objetividade - como o não-idêntico - no âmbito da razão.<br>The thesis of the priority of the object, essential to Adorno's non dogmatic materialism, is analyzed in its constitutive elements, as a criticism of idealism which is present mainly at the works Dialectic of enlightenment and Negative dialectic. As a criticism of idealism, particularly on the relationships between reason and experience as first developed from Kant to Hegel, the thesis is based on Lukács, Benjamin, and Horkheimer contributions and is embedded on the perspectives of Marx and Nietzsche. With its disruption of symmetry between subject and object, the thesis of the priority of the object reveals the frailty of Habermas assertion, in his Philosophical discourse of modernity, of Adorno's and Horkheimer's skepticism towards reason. The present author argues that, in opposition to this claim, Adorno and Horkheimer contributed, with their new way of relating historical material and theoretical approach, to the analysis of the problem of reification in its relations to objectivity - as the non-identical - within the realm of reason, and not outside of it