RESUMEN
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 (>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.
Asunto(s)
Síndrome de Cornelia de Lange , Proteínas Nucleares , Humanos , Proteínas Nucleares/genética , Síndrome de Cornelia de Lange/diagnóstico , Síndrome de Cornelia de Lange/genética , Síndrome de Cornelia de Lange/patología , Factores de Transcripción/genética , Proteínas de Ciclo Celular/genética , Fenotipo , Mutación , Genómica , Estudios de Asociación Genética , Factores de Elongación Transcripcional/genética , Histona Desacetilasas/genética , Proteínas Represoras/genéticaAsunto(s)
Ensayos Clínicos como Asunto/ética , Investigación Biomédica Traslacional/ética , Poblaciones Vulnerables , Aprobación de Drogas , Análisis Ético , Salud Global , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto/ética , Equivalencia Terapéutica , Experimentación Humana Terapéutica/ética , Estados UnidosRESUMEN
The purpose of this section's report is to propose strategies which will help those committed to promoting and implementing higher standards in dental education. There is a wide variety of systems throughout the world. These systems are developed, governed, operated and applied differently. Their standards, whether they are controlled by governments (federal and/or state), councils, universities or professional organizations are frequently determined cooperatively with dental educators, so that there is often some agreement among interested constituencies as to the content and application of the standards. These standards, whether they be called 'accreditation standards"requirements' or 'guidelines' (formal or informal), or written as laws or statutes reflect a region's history, traditions, culture and socio-economic realities. The emphasis in this report will be on the development of an organic or growing electronic database containing worldwide information relating to standards in dental education. This database might contain or be linked with similar sources detailing, inter alia, best practices, innovations and core values as they relate to the convergence of standards in education, professional training, continuous quality analysis, assessment and outcome. The linking of such a database to others containing electronic curricular modules, clinical management and practice information needs to be further developed.
