Identification of novel driver risk genes in CNV loci associated with neurodevelopmental disorders.

Copy-number variants (CNVs) are genome-wide structural variations involving the duplication or deletion of large nucleotide sequences. While these types of variations can be commonly found in humans, large and rare CNVs are known to contribute to the development of various neurodevelopmental disorders (NDDs), including autism spectrum disorder (ASD). Nevertheless, given that these NDD-risk CNVs cover broad regions of the genome, it is particularly challenging to pinpoint the critical gene(s) responsible for the manifestation of the phenotype. In this study, we performed a meta-analysis of CNV data from 11,614 affected individuals with NDDs and 4,031 control individuals from SFARI database to identify 41 NDD-risk CNV loci, including 24 novel regions. We also found evidence for dosage-sensitive genes within these regions being significantly enriched for known NDD-risk genes and pathways. In addition, a significant proportion of these genes was found to (1) converge in protein-protein interaction networks, (2) be among most expressed genes in the brain across all developmental stages, and (3) be hit by deletions that are significantly over-transmitted to individuals with ASD within multiplex ASD families from the iHART cohort. Finally, we conducted a burden analysis using 4,281 NDD cases from Decipher and iHART cohorts, and 2,504 neurotypical control individuals from 1000 Genomes and iHART, which resulted in the validation of the association of 162 dosage-sensitive genes driving risk for NDDs, including 22 novel NDD-risk genes. Importantly, most NDD-risk CNV loci entail multiple NDD-risk genes in agreement with a polygenic model associated with the majority of NDD cases.

Neumotórax espontáneo / Spontaneous pneumothorax

Introducción: El neumotórax espontáneo es la causa más frecuente de ingreso urgente en los servicios de cirugía torácica. Objetivo: Caracterizar a pacientes ingresados con diagnóstico de neumotórax espontáneo. Métodos: Se realizó un estudio descriptivo de 93 pacientes con diagnóstico clínico y radiológico de neumotórax espontáneo, se establecieron las variables del estudio y se utilizaron frecuencias absolutas y porcentajes. Para la asociación de las variables se empleó el estadígrafo ji cuadrado con un nivel de confiabilidad del 95 por ciento. Resultados: Predominó el neumotórax espontáneo primario (65,5 por ciento), el sexo masculino fue el más afectado (80,6 por ciento), con mayor frecuencia en el hemitórax derecho (72,2 por ciento) y el tabaquismo como antecedente (83,9 por ciento). La pleurostomía mínima fue el tratamiento definitivo en el 72 por ciento de los pacientes. La complicación más frecuente después de la pleurostomía, fue la fuga persistente de aire. El tratamiento quirúrgico con pleurodesis mecánica, ofreció un 100 por ciento de efectividad. La mortalidad quirúrgica fue nula. Conclusiones: El neumotórax espontáneo predomina en el sexo masculino en una proporción de 4,2:1, en pacientes menores de 40 años de edad. El antecedente patológico personal que más se asocia es la enfermedad pulmonar obstructiva crónica. El síntoma predominante es el dolor torácico. El neumotórax espontáneo primario fue más frecuente y el hemitórax derecho el más afectado. El tabaquismo está presente como antecedente en ambos tipos de neumotórax espontáneo. La modalidad de tratamiento más utilizada es la pleurostomía mínima(AU)

Introduction: Spontaneous pneumothorax is the most frequent cause of urgent admission to thoracic surgery services. Objective: To characterize patients admitted with a diagnosis of spontaneous pneumothorax. Methods: A descriptive study of 93 patients with a clinical and radiological diagnosis of spontaneous pneumothorax was carried out, the study variables were established and absolute frequencies and percentages were used. For the association of the variables, the chi square statistic was used with a confidence level of 95 percent. Results: Primary spontaneous pneumothorax predominated (65.5 percent), the male sex was the most affected (80.6 percent), with greater frequency in the right hemithorax (72.2 percent) and smoking as the antecedent (83.9 percent). Minimal pleurostomy was the definitive treatment in 72 percent of the patients. The most frequent complication after pleurostomy was persistent air leak. Surgical treatment with mechanical pleurodesis offered 100 percent effectiveness. There was not surgical mortality. Conclusions: Spontaneous pneumothorax predominated in males in a ratio of 4.2: 1, in patients under 40 years of age. The most associated personal pathological history was chronic obstructive pulmonary disease. The predominant symptom was chest pain. Primary spontaneous pneumothorax was more frequent and the right hemithorax the most affected. Smoking was present as a history in both types of spontaneous pneumothorax. The most widely used treatment modality was minimal pleurostomy(AU)