ABSTRACT
Background: Steroid-resistant nephrotic syndrome is the second leading cause of chronic kidney disease among patients <25 years of age. Through whole exome sequencing, identification of >65 monogenic causes has rendered insights into disease mechanisms of nephrotic syndrome. Methods: To elucidate novel monogenic causes of NS, we combined homozygosity mapping with ES in a worldwide cohort of 1649 pediatric patients with NS. Results: We identified homozygous missense variants in MYO1C in two unrelated children with nephrotic syndrome (c.292C>T, p.R98W; c.2273 A>T, p.K758M). We evaluated publicly available kidney single-cell RNA sequencing datasets and found MYO1Cto be predominantly expressed in podocytes. We then performed structural modeling in molecular viewer PyMol using the super function aligning shared regions within both partial structures of MYO1C (4byf and 4r8g). In both structures, calmodulin, a common regulator of myosin activity, is shown to bind to the IQ motif. At both residue sites (K758; R98), there are ion-ion interactions stabilizing intradomain and ligand interactions: R98 binds to nearby D220 within the Myosin Motor Domain and K758 binds to E14 on a calmodulin molecule. Variants of these charged residues to non-charged amino acids could ablate these ionic interactions, weakening protein structure and function establishing the impact of these variants. Conclusion: We here identified recessive variants in MYO1C as a potential novel cause of nephrotic syndrome in children.
ABSTRACT
Background: Malnutrition increases the risk of developing tuberculosis (TB) and causes reactivation of latent pulmonary TB. On the other hand, TB is a recognized cause of malnutrition. Evaluation of the nutritional status and anemia of tuberculous patients with active disease is an important step toward TB management.The objectives of the study were to determine the nutritional status and patterns of anemia in adult patients with active pulmonary TB. Methods: A.cross-sectional hospital-based study was performed on newly diagnosed patients with sputum-positive pulmonary TB. The nutritional status, total percentage of body fat (BF%), anemia, and general health of each patient were assessed with measurements of the body mass index (BMI), skin fold thickness, complete blood counts, and biochemical tests. Results: Patients' ages ranged from 16- to 74-year old, with the majority between 20- and 40-year old. Male: female ratio was 2:1. The majority of males and females (91.2% and 84.5%, respectively) had low BF%. Underweight (BMI < 18.5) was 62%, whereas overweight (BMI ≥25.0) was 4%. BMI showed a significant decline with chronicity of the illness (P < 0.001). Eighty participants showed anemia, 90% microcytic hypochromic, and 10% normocytic normochromic. Serum albumin was low in 21%, with no relation to renal disease and insignificant association with proteinuria. Conclusion: Patients with active pulmonary TB are likely to have microcytic hypochromic anemia, low BF%, and low BMI, especially with a long duration of the disease.
