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

Clinical validity assessment of genes frequently tested on intellectual disability/autism sequencing panels.

[en] PURPOSE: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not. METHODS: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship. RESULTS: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants. CONCLUSION: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs

Some bounds on reliability of coherent systems of IFRA components

In this paper we find new bounds for the reliability of coherent systems of independent components with increasing failure rate average (IFRA) lifetimes. These bounds are based on certain bounds available for the survival functions of IFRA random variables and the fact that the IFRA class of life distributions is closed under the formation of coherent systems. These bounds are compared with other applicable bounds in this case. An illustration of explicit computations of the bounds is provided for the bridge structure with components having independent gamma life distributions.</jats:p

Identify etiology of morbidity events of earlier children among multigravida women

Morbidity condition are more prevalent in the children who are exposed to various risk factors like overcrowding, poor nutrition etc. morbidity in the children residing in the rural area is more as compared to the urban area.Because socio-economical strata and standard of living, inadequate knowledge.Children are the future of any healthy nation they are asset of nation, unfortunately this assets falls children, because of poor maintenance of health, Malaria and acute respiratory infection are higher among children in rural setting and children whose mothers are 16–17 and 28–33 years of age. Objective: To identify the etiology of morbidity events of earlier children among multigravida women. Research Methodology: The quantitative approach and community based cross-sectional study design was used. Were enrolled 492 multigravida women with her 992 earlier children from 0-18 yr age group with used simple random sampling technique, Analyses was done using SPSS version 26.00 and identify etiology events of earlier children among multigravida women. Result: major finding identify etiology of morbidity events of earlier children among multigravida women’s group was G2P2 in that; 1(0.2%) illness having before pregnancy in multigravida women and having illness during pregnancy, 23(3.8%) were taken treatment during pregnancy, 50(8.2%) women were having consanguinity marriage

Mental state and emotion detection from musically stimulated EEG

Abstract This literature survey attempts to clarify different approaches considered to study the impact of the musical stimulus on the human brain using EEG Modality. Glancing at the field through various aspects of such studies specifically an experimental protocol, the EEG machine, number of channels investigated, feature extracted, categories of emotions, the brain area, the brainwaves, statistical tests, machine learning algorithms used for classification and validation of the developed model. This article comments on how these different approaches have particular weaknesses and strengths. Ultimately, this review concludes a suitable method to study the impact of the musical stimulus on brain and implications of such kind of studies

Whole Exome Sequencing detects PYGM variants in two adults with McArdle disease

McArdle disease is a progressive and debilitating glycogen storage disease with typical onset in late childhood. Here we describe a former competitive athlete with early adult onset McArdle disease and a septuagenarian with a history of exercise-intolerance since adolescence who was evaluated for proximal muscle weakness. Exome sequencing identified bi-allelic variants in PYGM gene for both cases. The former athlete has the common, well-known pathogenic variant p.(Arg50Ter) in trans with a novel missense variant, p.(Asp694Glu). The second individual has a previously described homozygous missense variant, p.(Arg771Gln). Here, we describe the clinical course, enzyme-testing results using muscle tissue and molecular findings for the individuals, and add to the knowledge of the genotypic spectrum of this disorder.</jats:p