Neuromuscular disorders (NMDs) affect approximately 1 in 1,000 individuals and are clinically and genetically heterogeneous. Despite advances in genomic diagnostics, many cases remain unsolved after initial sequencing. Bioinformatic reanalysis approaches provide opportunities to identify missed variants and establish novel disease genes.

Genes that enhance T-cell function represent promising targets for improving engineered T-cell therapies for cancer. While extensive CRISPR knockout screens have identified key genes enhancing T-cell persistence, employing Sleeping Beauty (SB) insertional mutagenesis, which induces both gain-of-function (GOF) and loss-of-function (LOF) mutations via the generation of fusion transcripts with endogenous genes, may uncover additional critical factors that previous approaches have overlooked.

Pancreatic cancer carries a poor prognosis, with few effective treatment options available. Various rearranged during transfection (RET) proto-oncogene fusions have been found in a small fraction of pancreatic cancers; however, the hook microtubule tethering protein 3 (HOOK3)-RET fusion has not yet been reported in the medical literature.

Epilepsy syndromes are clinically defined by their specific set of features, including seizure types, age at onset, electroencephalographic patterns, and prognosis. For example, autosomal-dominant lateral temporal lobe epilepsy (ADLTE) is a well-recognized epilepsy syndrome associated with heterozygous leucine-rich glioma inactivated-1 (LGI1) gene variants.

Progressive supranuclear palsy (PSP) is a rare and devastating tauopathy with limited global data. Given India’s large population, genetic diversity, and clinical heterogeneity, large multicenter datasets are crucial to enrich global understanding of PSP.

Childhood and adolescent obesity are growing global health concerns, with genetic factors playing an important role. Despite the increasing prevalence of obesity in India, monogenic obesity remains underdiagnosed. We report 2 cases of early-onset morbid obesity due to melanocortin-4 receptor (MC4R) gene mutation. Case 1 was a 5-year-old boy who presented with severe hyperphagia and rapid weight gain since infancy. Case 2 was a 12-year-old girl who presented with progressive obesity, hyperphagia, and bilateral genu varum.

In 2016, a 19-year-old man developed severe muscle cramps following a diarrheal illness. On evaluation, he was found to have deranged kidney function and referred to nephrology. At the time of referral, his creatinine level was 213.04 μmol/l (2.41 mg/dl) (estimated glomerular filtration rate, 36 ml/min per 1.73 m2), with bland urine sediment, and a blood pressure of 100/60 mm Hg. Physical examination was unremarkable. Investigations showed hypomagnesemia (Supplementary Table S1).

DYT-ANO3 is an autosomal dominant dystonia syndrome caused by pathogenic variants in the ANO3 gene, typically presenting as focal or segmental dystonia of the neck and upper limbs, often accompanied by tremor. However, the clinical spectrum has broadened to include a variety of movement phenotypes. Here, we report a large Indian family harbouring a novel ANO3 variant, demonstrating wide phenotypic heterogeneity.

Sarcomas exhibit clinicopathologic heterogeneity, leading to diagnostic and therapeutic uncertainty. This study assesses the clinical value of integrating targeted RNA-based next-generation sequencing (NGS) into a multidisciplinary sarcoma workflow to improve diagnosis, enable comprehensive molecular characterization, and inform personalized treatment strategies.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) and X-Linked Alport Syndrome (AS) are the most common monogenic causes of chronic kidney disease (CKD), each capable of independently leading to end-stage kidney disease (ESKD). However, the concurrent presence of both disorders in a single individual is exceedingly rare and poses significant diagnostic complexity.