Publications by authors named "Kabra M"

Background: Megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare and progressive neurodegenerative disorder involving the white matter, is not adequately recapitulated by current disease models. Somatic cell reprogramming, along with advancements in genome engineering, may allow the establishment of human models of MLC for disease modeling and drug screening. In this study, we utilized cellular reprogramming and gene-editing techniques to develop induced pluripotent stem cell (iPSC) models of MLC to recapitulate the cellular context of the classical MLC-impacted nervous system.

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Objectives: This study aims to describe the indications, complications, yield, and safety of amniocentesis beyond 24 weeks for prenatal diagnostic procedures along with the associated maternal and fetal outcomes.

Methods: A retrospective analysis was conducted on 60 pregnant women (with 61 fetuses) who underwent amniocentesis at or beyond 24 weeks from March 2021 to June 2023 at a tertiary care referral center. Data was collected from medical records and individual patient followups.

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Objective: Glycogen storage disorders (GSD), inherent disorders of carbohydrate metabolism, feature hypoglycemia as a hallmark. Normoglycemia and glucose monitoring are pivotal in disease management. Conventional glucometer-based monitoring may overlook hypoglycemic trends.

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The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23-42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor.

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Article Synopsis
  • The study aimed to assess molecular changes at the 11p15.5 locus in 32 patients with isolated lateralized overgrowth (ILO).
  • Methylation-sensitive analyses revealed aberrations in 28% of patients, with some showing features similar to Silver Russell syndrome (SRS) and uniparental disomy (UPD) in 9% of cases, though patients did not fully meet SRS criteria.
  • The findings suggest that ILO could be a mild variant of Beckwith-Wiedemann syndrome (BWS), with significant implications for patient monitoring and diagnosis.
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Mitochondrial disorders are a diverse group of diseases caused by mutations in genes encoded by either nuclear or mitochondrial DNA. In a group of patients with nuclear mitochondriopathies, the authors analysed the clinico-radiological and genotypic spectrum. The study included 25 patients with a genetic diagnosis of nuclear mitochondrial cytopathy who were seen over a 5 y period.

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  • Primary congenital glaucoma (PCG) is a genetic eye condition in children caused by abnormalities in eye structures, and past research has linked certain rare genetic variants to its complexity and variability.
  • A study involving deep sequencing of a core centrosomal protein in a group of PCG patients revealed rare pathogenic variants in a small percentage of cases, with some co-occurring genetic variations leading to poorer outcomes.
  • The findings point to the possible roles of additional genes and cilia-centrosomal functions in the development of PCG, suggesting further areas for research in understanding this condition.
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Lysinuric protein intolerance (LPI) is an inborn metabolic error caused by cationic amino acid transport defects. The disease has a significant degree of phenotypic variation, with no confirmed genotype-phenotype correlation. Because it presents with symptoms similar to far more common diseases, the diagnosis is often missed, resulting in increased morbidity and mortality.

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Storage disorders are a group of inborn errors of metabolism caused by the defective activity of lysosomal enzymes or transporters. All of these disorders have multisystem involvement with variable degrees of neurological features. Neurological manifestations are one of the most difficult aspects of treatment concerning these diseases.

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Distal arthrogryposis type 5D (DA5D) is clinically characterized by knee extension contractures, distal joint contractures, clubfoot, micrognathia, ptosis, and scoliosis. We report nine affected individuals from eight unrelated Indian families with DA5D. Although the overall musculoskeletal phenotype is not very distinct from other distal arthrogryposis, the presence of fixed knee extension contractures with or without scoliosis could be an important early pointer to DA5D.

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Skeletal dysplasias or osteochondrodysplasias comprise a large heterogeneous group of genetic disorders and possess significant overlap on imaging, which adds to the dilemma of the reporting radiologist. These entities are routinely evaluated with a detailed skeletal survey and hand radiographs form a crucial part of a complete survey. Certain conditions have characteristic imaging findings that enable a diagnosis be made on hand radiograph alone.

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Motor neurons are the final common pathway through which the brain controls movement of the body, forming the basic elements from which all movement is composed. Yet how a single motor neuron contributes to control during natural movement remains unclear. Here we anatomically and functionally characterize the individual roles of the motor neurons that control head movement in the fly, Drosophila melanogaster.

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Article Synopsis
  • Genomic analysis of an infant suspected to have a mitochondrial disorder revealed a significant deletion in two genes (ERCC8 and NDUFAF2) that likely contributed to the infant's health issues.
  • Studies using fetal-derived fibroblast cells showed reduced energy production and mitochondrial dysfunction, aligning with the observed symptoms and the infant's death.
  • The research highlighted the benefits of whole-genome sequencing by creating a specific test for family carrier screening and enabling prenatal testing, resulting in the successful birth of two healthy children.
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Split-hand/foot malformation (SHFM) is a genetically heterogeneous congenital limb reduction defect characterized by the deficiencies of central rays of the autopod. Tandem duplications at 10q24 locus account for approximately 20% of all SHFM cases. Here, we report five affected individuals from four unrelated Indian families with SHFM3 caused by microduplication of 10q24 locus showing varied clinical presentations.

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Background: Minimally invasive autopsy (MIA) using post-mortem magnetic resonance imaging with ancillary investigations is reported as accurate as conventional autopsy. This study assesses MIA's feasibility and accuracy compared to conventional autopsy.

Method: MIA and/or conventional autopsy were performed on malformed fetuses (14-20 weeks gestation) and stillbirths (>20 weeks gestation), with/without malformation.

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Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review.

Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks.

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Objectives: To evaluate the natural history and to highlight the possible masqueraders causing diagnostic delay and iatrogenic interventions in Fibrodysplasia Ossificans Progressiva (FOP).

Methods: Patient details with suspected FOP were retrieved from the patient registry from 2012 through 2021. Clinical records, X-rays, clinical photographs, and molecular testing results were captured.

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Interpenetrating polymer networks (IPNs) are a class of materials with interwoven polymers that exhibit unique blended or enhanced properties useful to a variety of applications, ranging from restorative protective materials to conductive membranes and hydrophobic adhesives. The IPN formation kinetics can play a critical role in the development of the underlying morphology and in turn the properties of the material. Dual photoinitiation of copper-catalyzed azide-alkyne (CuAAC) and radical mediated methacrylate polymerization chemistries enable the manipulation of IPN microstructure and properties by controlling the kinetics of IPN formation via the intensity of the initiating light.

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Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant skeletal dysplasia characterised by swelling and restriction of movement in the wrist and ankle joints, as well as osteolysis of the carpal and tarsal bones, that can be misdiagnosed as juvenile idiopathic arthritis. We describe five Indian families with heterozygous nonrecurrent missense pathogenic variants in exon 1 of MAF bZIP transcription factor B (MAFB).

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Clinical genome editing is emerging for rare disease treatment, but one of the major limitations is the targeting of CRISPR editors' delivery. We delivered base editors to the retinal pigmented epithelium (RPE) in the mouse eye using silica nanocapsules (SNCs) as a treatment for retinal degeneration. Leber congenital amaurosis type 16 (LCA16) is a rare pediatric blindness caused by point mutations in the KCNJ13 gene, a loss of function inwardly rectifying potassium channel (Kir7.

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Article Synopsis
  • Bardet-Biedl syndrome (BBS) is a rare genetic disorder with symptoms like vision problems, obesity, extra fingers/toes, urogenital issues, and cognitive challenges.
  • A study of 108 BBS patients in India found a high occurrence of variations in the BBS10 and BBS1 genes, along with a potentially new gene, TSPOAP1.
  • The research highlights a unique genetic profile for BBS in this Indian cohort, with a notable 36% presence of digenic variants, suggesting the importance of genetic testing for accurate diagnosis and understanding of the disease.
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Objectives: To study the clinical and molecular spectrum of Methylmalonic acidemia (MMA).

Methods: In this retrospective study, the records of 30 MMA patients were evaluated for their phenotype, biochemical abnormalities, genotype, and outcomes.

Results: Thirty patients with MMA (age range 0-21 y) from 27 unrelated families were enrolled.

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SARS-CoV-2 evolution has continued to generate variants, responsible for new pandemic waves locally and globally. Varying disease presentation and severity has been ascribed to inherent variant characteristics and vaccine immunity. This study analyzed genomic data from 305 whole genome sequences from SARS-CoV-2 patients before and through the third wave in India.

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