A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.

EDSS1, a syndrome characterized by ectodermal dysplasia-syndactyly, is inherited in an autosomal recessive manner due to mutations in the NECTIN4/PVRL4 gene. Clinical manifestations of the syndrome include defective nail plate, sparse to absent scalp and body hair, spaced teeth with enamel hypoplasia, and bilateral cutaneous syndactyly in the fingers and toes. Here, we report a consanguineous family of Kashmiri origin presenting features of EDSS1. Using whole exome sequencing, we found a recurrent nonsense mutation (NM_030916: c.181C > T, p.(Gln61 ∗)) in the NECTIN4 gene. The variant segregated perfectly with the disorder within the family. The candidate variant was absent in 50 in-house exomes pertaining to other disorders from the same population. In addition to the previously reported clinical phenotype, an upper lip cleft was found in one of the affected members as a novel phenotype that is not reported by previous studies in EDSS1 patients. Therefore, the study presented here, which was conducted on the Kashmiri population, is the first to document a NECTIN4 mutation associated with the upper lip cleft as a novel phenotype. This finding broadens the molecular and phenotypic spectrum of EDSS1.

Role of iron in the reduction of anemia among women of reproductive age in low-middle income countries: insights from systematic review and meta-analysis.

BACKGROUND: Iron deficiency anemia is a common public health issue among women of reproductive age (WRA) because it can result in adverse maternal and birth outcomes. Although studies are undertaken to assess iron efficacy, some gaps and limitations in the existing literature need to be addressed. To fill the gaps, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) assessing the role of iron in reducing anemia among WRA in low-middle-income countries (LMICs). METHODS: A comprehensive search strategy was used to search Medline through PubMed, Embase, and Science Direct for RCTs published between 2000 and 2020. The primary outcome was the mean change in hemoglobin level. We used standardized mean differences and their respective 95% CI to estimate the pooled effect. We used I2 statistics and Egger's test to assess heterogeneity and publication bias, respectively. This review was carried out in accordance with revised guidelines based on the Preferred Reporting Items for Systematic Review and Meta-analysis. RESULTS: The findings showed that iron therapy improved hemoglobin and ferritin levels, though the results varied across studies. An overall pooled effect estimate for the role of iron therapy in improving the hemoglobin levels among WRA was -0.71 (95% CI: -1.27 to -0.14) (p = 0.008). Likewise, the overall pooled effect estimate for the role of iron therapy in improving the ferritin levels among WRA was -0.76 (95% CI: -1.56 to 0.04) (p = 0.04). The heterogeneity (I2) across included studies was found to be statistically significant for studies assessing hemoglobin (Q = 746.93, I2 = 97.59%, p = 0.000) and ferritin level (Q = 659.95, I2 = 97.88%, p = 0.000). CONCLUSION: Iron therapy in any form may reduce anemia's burden and improve hemoglobin and ferritin levels, indicating improvement in iron-deficiency anemia. More evidence is required, however, to assess the morbidity associated with iron consumption, such as side effects, work performance, economic outcomes, mental health, and adherence to the intervention, with a particular focus on married but non-pregnant women planning a pregnancy in the near future. TRIAL REGISTRATION: Registered with PROSPERO and ID is CRD42020185033.

Outcomes in Lower Pole Kidney Stone Management Using Mini-Percutaneous Nephrolithotomy Compared With Retrograde Intra Renal Surgery: A Randomized Controlled Trial.

Background Because of the anatomical properties of the inferior calyx, lower pole stones are difficult to remove through the ureter, even if the stones are fragmented. Retrograde intra-renal surgery (RIRS) is typically employed to treat the smaller lower pole stones (1.0-2.0 cm) while percutaneous nephrolithotomy (PCNL) is primarily used to treat the larger diameter stones or when RIRS has failed to clear the stones. This study was conducted to compare mini-PCNL and RIRS for the management of lower pole kidney stones in terms of stone clearance. Material and methods This randomized control trial was conducted in the Department of Urology, Shaikh Zayed Hospital, Lahore from October 2020 to December 2022. A total of 150 patients between the ages of 18 and 80 years with a kidney stone size of 10-20 mm at the lower pole were included. Patients with positive urine culture, anatomical abnormalities, uncontrolled diabetes (hemoglobin{Hb}A1c >9%), and undergone previous renal surgery were excluded. Group A patients were treated with mini-PCNL, while group B patients were managed with RIRS. Follow-up visits were planned four weeks postoperatively with CT KUB (computed tomography of kidneys, ureters, and bladder) plain to assess stone clearance. Results The mean age in group A was 43.27 ± 13.86 years, while in group B was 45.32 ± 14.14 years. Out of 150 patients, 102 (68.0%) were males and 48 (32.0%) were females. Mean size of the stone was 15.30 ± 2.21 mm. Stone clearance after mini-PCNL was found in 69 (92.0%) patients and after RIRS in 59 (78.67%) patients (p-value = 0.021). Mean hospital stay after RIRS was 1.1 ± 0.09 days, while it was 2.3 ± 0.64 days after mini-PCNL (p-value < 0.001). Two (2.67%) patients in the mini-PCNL group developed bleeding postoperatively. The stone clearance rate in older patients (51 to 80 years) was significantly higher in the mini-PCNL group than RIRS group. Similarly, the stone clearance rate in female patients and in patients with larger stones (16 to 20 mm) was found to be higher in mini-PCNL group as compared to the RIRS group. Conclusion This study concluded that both mini-PCNL and RIRS are safe and efficient techniques for treating lower pole kidney stones with a size of 11-15 mm. However, mini-PCNL has a higher stone clearance rate compared to RIRS in the treatment of stones larger than 15 mm in size. This study further suggested that patients treated with mini-PCNL had a longer hospital stay compared to patients treated with RIRS.

Evaluation of Standard Loose Plastic Packaging for the Management of Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebriondiae).

Three standard foodstuff plastic packaging namely polyethylene (PE), polypropylene (PP), and polyvinylchloride (PVC) were evaluated for management of lesser grain borer Rhyzopertha dominica (F.) (Coleoptera: Bostrichidae) and red flour beetle Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Resistance parameters in packaging were recorded as punctures, holes, penetrations, sealing defects, and invasions with two thicknesses and tested for two lengths of time. Damages like punctures, holes and penetrations by both insects were more in PE packaging however R. dominica made more penetrations in PP than in PE. For both insects sealing defects and invasions were predominant in PVC than in others. Thickness did not affect significantly damage types but significantly more holes and penetrations by R. dominica were in less thickness. Punctures and holes by R. dominica were more after less time period but other damages in packaging were more after more time period. However for T. castaneum all sorts of damages were seen more after more time period. Overall categorization between two insects showed R. dominica made more penetrations and T. castaneum made more invasions compared with their counterparts. Pictures were taken under camera fitted microscope to magnify punctures and holes in different packaging and thicknesses. Insect mortality due to phosphine was more in PP and PE packaging and least in PVC packaging and thickness effect was marginal. T. castaneum mortality was significantly more after 48 h than after 24 h. Damages extent in packaging and fumigation results showed PP to be the best of three packaging materials to manage these insects.

A novel missense mutation in the ectodysplasin-A (EDA) gene underlies X-linked recessive nonsyndromic hypodontia.

BACKGROUND: Nonsyndromic hypodontia or congential absence of one or more permanent teeth is a common anomaly of dental development in humans. This condition may be inherited in an autosomal (dominant/recessive) or X-linked (dominant/recessive) mode. Mutations in three genes, PAX9, MSX1, and AXIN2, have been determined to be associated with autosomal dominant and recessive tooth agenesis. Recent studies in a few families showed that mutations in the ectodysplasin A (EDA) gene result in X-linked nonsyndromic hypodontia. METHODS: Genotyping of a five-generation Pakistani family with X-linked isolated hypodontia having three affected men was carried out using EDA-linked polymorphic microsatellite markers on chromosome Xq12-q13.1. To screen for a mutation in the EDA gene, all of its coding exons and splice junction sites were PCR amplified from genomic DNA of affected and unaffected individuals of the family and sequenced directly in an ABI Prism 310 automated DNA sequencer. RESULTS: We successfully mapped the affected locus to chromosome Xq12-q13.1, and found a novel missense mutation (c.993G>C) in the EDA gene in the affected men. The mutation causes substitution of glutamine with histidine (p.Q331H) in the tumor necrosis factor homology domain of EDA. CONCLUSIONS: A mutation identified in this study extends the body of evidence implicating the EDA gene in X-linked nonsyndromic hypodontia and supports the role of EDA-EDAR-EDARADD signaling in the morphogenesis of teeth.

A homozygous nonsense mutation in the human desmocollin-3 (DSC3) gene underlies hereditary hypotrichosis and recurrent skin vesicles.

Desmosomes are the major players in epidermis and cardiac muscles and contribute to intercellular binding and maintenance of tissue integrity. Two important constituents of desmosomes are transmembrane cadherins named desmogleins and desmocollins. The critical role of these desmosomal proteins in epithelial integrity has been illustrated by their disruption in mouse models and human diseases. In the present study, we have investigated a large family from Afghanistan in which four individuals are affected with hereditary hypotrichosis and the appearance of recurrent skin vesicle formation. All four affected individuals showed sparse and fragile hair on scalp, as well as absent eyebrows and eyelashes. Vesicles filled with thin, watery fluid were observed on the affected individuals' scalps and on most of the skin covering their bodies. A scalp-skin biopsy of an affected individual showed mild hair-follicle plugging. Candidate-gene-based homozygosity linkage mapping assigned the disease locus to 8.30 cM (8.51 Mbp) on chromosome 18q12.1. A maximum multipoint LOD score of 3.30 (theta = 0.00) was obtained at marker D18S877. Sequence analysis of four desmoglein and three desmocollin genes, contained within the linkage interval, revealed a homozygous nonsense mutation (c.2129T>G [p.Leu710X]) in exon-14 of the desmocollin-3 (DSC3) gene.