Homozygous Missense Variants in NTNG2, Encoding a Presynaptic Netrin-G2 Adhesion Protein, Lead to a Distinct Neurodevelopmental Disorder.

NTNG2 encodes netrin-G2, a membrane-anchored protein implicated in the molecular organization of neuronal circuitry and synaptic organization and diversification in vertebrates. In this study, through a combination of exome sequencing and autozygosity mapping, we have identified 16 individuals (from seven unrelated families) with ultra-rare homozygous missense variants in NTNG2; these individuals present with shared features of a neurodevelopmental disorder consisting of global developmental delay, severe to profound intellectual disability, muscle weakness and abnormal tone, autistic features, behavioral abnormalities, and variable dysmorphisms. The variants disrupt highly conserved residues across the protein. Functional experiments, including in silico analysis of the protein structure, in vitro assessment of cell surface expression, and in vitro knockdown, revealed potential mechanisms of pathogenicity of the variants, including loss of protein function and decreased neurite outgrowth. Our data indicate that appropriate expression of NTNG2 plays an important role in neurotypical development

Does high-frequency chest wall oscillation therapy have any impact on the infective exacerbations of chronic obstructive pulmonary disease? A randomized controlled single-blind study

Objective: To investigate the impact of high-frequency chest wall oscillation in chronic obstructive pulmonary disease patients with infective exacerbation

Biallelic variants in KIF14 cause intellectual disability with microcephaly

Kinesin proteins are critical for various cellular functions such as intracellular transport and cell division, and many members of the family have been linked to monogenic disorders and cancer. We report eight individuals with intellectual disability and microcephaly from four unrelated families with parental consanguinity. In the affected individuals of each family, homozygosity for likely pathogenic variants in KIF14 were detected; two loss-of-function (p.Asn83Ilefs*3 and p.Ser1478fs), and two missense substitutions (p.Ser841Phe and p.Gly459Arg). KIF14 is a mitotic motor protein that is required for spindle localization of the mitotic citron rho-interacting kinase, CIT, also mutated in microcephaly. Our results demonstrate the involvement of KIF14 in development and reveal a wide phenotypic variability ranging from fetal lethality to moderate developmental delay and microcephaly

The Circulating Levels of Selenium, Zinc, Midkine, Some Inflammatory Cytokines, and Angiogenic Factors in Mitral Chordae Tendineae Rupture

Chordae tendineae rupture process is associated with increased production of inflammatory and angiogenesis mediators in connective tissues, which contributes to chronic inflammation and pathogenesis of degenerative chordae. A few trace elements are known to possess antioxidant, anti-inflammatory, and antiangiogenic properties. Therefore, the aim of this study was to determine whether zinc, selenium, midkine (MK), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-alpha (TNF-alpha), vascular endothelial growth factor-A (VEGF-A), platelet-derived growth factor-BB (PDGF-BB), and reduced glutathione (GSH) levels are associated with inflammation and angiogenesis processes in the context of a potential etiology causing aggravation of mitral regurgitation and/or ruptured chordae tendineae. Seventy-one subjects comprising 34 patients with mitral chordae tendineae rupture (MCTR) and 37 healthy controls diagnosed on the basis of their clinical profile and transthoracic echocardiography were included in this study. The levels of GSH, MK, selenium, and zinc were found to be lower in the patients group when compared to control group. There were no significant difference in plasma TNF-alpha, IL-1 beta, IL-6, IL-8, VEGF-A, and PDGF-BB levels between two groups. There were positive significant correlations between MK and GSH, MK, and selenium levels in patients with MCTR. According to our data in which selenium, zinc, MK, and GSH decreased in MCTR patients, inflammatory response, oxidative stress, and trace element levels may contribute to etiopathogenesis of mitral regurgitation and/or ruptured chordae tendineae