9 research outputs found
Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.
Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Together with the previously reported cases, all 31 genomic deletions in 16q24.1, pathogenic for ACDMPV, for which parental origin was determined, arose de novo with 30 of them occurring on the maternally inherited chromosome 16, strongly implicating genomic imprinting of the FOXF1 locus in human lungs. Surprisingly, we have also identified four ACDMPV families with the pathogenic variants in the FOXF1 locus that arose on paternal chromosome 16. Interestingly, a combination of the severe cardiac defects, including hypoplastic left heart, and single umbilical artery were observed only in children with deletion CNVs involving FOXF1 and its upstream enhancer. Our data demonstrate that genomic imprinting at 16q24.1 plays an important role in variable ACDMPV manifestation likely through long-range regulation of FOXF1 expression, and may be also responsible for key phenotypic features of maternal uniparental disomy 16. Moreover, in one family, WES revealed a de novo missense variant in ESRP1, potentially implicating FGF signaling in the etiology of ACDMPV
Adoptive transfer of activated marrow-infiltrating lymphocytes induces measurable antitumor immunity in the bone marrow in multiple myeloma
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Test Performance Characteristics of the AIR, GAD-7 and HADS-Anxiety Screening Questionnaires for Anxiety in Chronic Obstructive Pulmonary Disease
Rationale: Anxiety is a common comorbidity of chronic obstructive pulmonary disease (COPD) that is associated with higher morbidity and mortality. We evaluated three anxiety screening questionnaires: the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A), and the Anxiety Inventory for Respiratory Disease (AIR).Objectives: To evaluate and compare the test performance characteristics of three anxiety screening questionnaires, using the Mini-International Neuropsychiatric Interview (MINI), version 7.0, as the "gold standard."Methods: Individuals with COPD were recruited at 16 centers. The MINI and questionnaires were administered by trained research coordinators at an in-person visit and readministered by telephone 2-4 weeks later. A composite score for the presence of any Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) anxiety disorder was computed, based on the MINI as the gold standard, compared with a participant screening positive on self-report measures for these analyses.Results: Two hundred and twenty eligible individuals with COPD were enrolled; 219 completed the study. Eleven percent were identified as having a DSM-V anxiety disorder, based on the MINI. Elevated anxiety symptoms based on questionnaires were 38% for the AIR, 30% for the GAD-7, and 20% for the HADS-A. Area under the receiver operating characteristic curve (AUC) was highest for the GAD-7 (0.78; 95% confidence interval [CI], 0.69-0.87), followed by the HADS-A (0.74; 95% CI, 0.64-0.84) and the AIR (0.66; 95% CI, 0.56-0.76). The AUC for the GAD-7 was significantly greater than for the AIR (P = 0.014). Sensitivity was not statistically different among the questionnaires: 77% for the GAD-7, 63% for the HADS-A, and 66% for the AIR. The HADS-A had the highest specificity, 85%, which was significantly higher than that of the GAD-7 (77%; P < 0.001) and the AIR (65%; P < 0.001); GAD-7 specificity was higher than AIR specificity (P < 0.001).Conclusions: Symptoms of anxiety among patients with COPD as identified by screening questionnaires were common and significantly higher than the prevalence of anxiety disorder meeting DSM-V criteria. The GAD-7, the HADS-A and the AIR questionnaires had fair to moderate psychometric properties as screening tools for anxiety in individuals with COPD, indicating the need for improved measures for this patient population