Megalencephalic leukoencephalopathy with subcortical cysts (MLC) has been described in the literature mostly as early-onset leukodystrophy with cerebellar ataxia being the main clinical phenotype. However, other associated movement disorders have also been reported discretely. Here, we present seven cases of MLC.

Next-generation sequencing has enabled non-invasive diagnosis of type IV collagen disease beyond the typical presentation of Alport syndrome (AS). A review of clinical and histological records from 2015-2023 identified 43 patients (34 boys) with 39 variants in COL4A5 (n = 27), COL4A4 (n = 7), and COL4A3 (n = 5), with X-linked, autosomal recessive, and autosomal dominant inheritance in 30, 8, and 5 patients, respectively. The median age and eGFR at diagnosis were 10 years and 100.1 ml/min/1.73 m². Fifteen patients initially presented with steroid-resistant nephrotic syndrome, and AS was suspected due to persistent hematuria, low eGFR, characteristic histology, and non-response to immunosuppression. Kidney biopsies revealed focal segmental glomerulosclerosis, minimal change disease, or mesangial proliferative glomerulonephritis. Electron microscopy confirmed glomerular basement membrane changes in 12 cases. Nearly half (48.8%) had sensorineural hearing loss, and 12 patients progressed to chronic kidney disease stages 4-5, with median survival of 15.6 years with eGFR > 30 ml/min/1.73 m². The AS phenotype varies from urinary abnormalities to more severe manifestations, with worse outcomes in boys with X-linked disease.

Multiple myeloma, a complex hematologic malignancy, causes severe bone loss, pain, and fractures that significantly impact patients’ quality of life and survival. This article reviews current biomarkers used for diagnosis and prognosis, from traditional serum markers to advanced molecular profiling techniques, highlighting their utility and limitations. It emphasizes the role of personalized medicine in tailoring therapies and explores the integration of genomic, proteomic, and next-generation sequencing data to better understand disease progression. The article provides valuable insights for clinicians and researchers to optimize patient care and improve therapeutic strategies.

Nine novel HLA alleles were identified when HLA typing individuals from the Indian population.

GNE myopathy is a rare, slowly progressive adult-onset distal myopathy with autosomal recessive inheritance, characterized by quadriceps sparing and preferential anterior tibial involvement. Most patients become wheelchair-bound 10-20 years after onset. This study retrospectively analyzed the phenotype-genotype characteristics and disease progression in 157 GNEM patients from a neurology referral hospital in southern India. The mean age at onset and diagnosis was 26.5±6.2 years and 32.8±7.8 years, respectively, with an Male to Female ratio of 25:13. The most common presenting symptom was foot drop (46.5%), with tibialis anterior involvement in 89.2% and early quadriceps weakness in 3.2%. The Indian Founder variant (c.2179 G>A, p.Val727Met) was identified in 82.2% of patients, predominantly in a compound heterozygous state, and was associated with a more severe phenotype. The study highlights genotype-clinical parameter relationships, suggesting that specific GNE genotypes could predict disease severity and progression.

Extended sequences for 13 HLA alleles were found which had limited coverage previously.

Cases of imported malaria are reported each year in several malaria non-endemic countries, including Kuwait. PCR testing is the ideal method for identification of the infecting Plasmodium spp. The present study documented the epidemiologic characteristics of molecularly confirmed cases of imported malaria in Kuwait during the first year of COVID-19 pandemic. Malaria diagnosis was made by microscopy of blood-stained smears and confirmed by a multiplex real-time PCR assay. Samples with discordant species identification results were sequenced. A total of 27 cases (27%) [P. falciparum, 14; P. vivax, 11; P. ovale, 1; mixed P. falciparum and P. malariae, 1] were detected, of whom 12 came to Kuwait for the first time and 15 were returning after visiting their home countries. Most of the returning travelers (12 out of 15 cases, 80%) had not received malaria chemoprophylaxis. Most cases of falciparum malaria (13/15) were Africans while most of the vivax cases (9/11) were Asians. Malaria was more common among subjects entering Kuwait for the first time (OR = 4.025, CI 1.07,15.1) and illiterates (OR = 13.8, CI 1.8,101.4). In conclusion, imported malaria caused mainly by P. falciparum and P. vivax was an ongoing problem during the COVID-19 pandemic. Travel history and education level were significant predictors of malaria among suspected cases.

The study analyzed the outcomes of comprehensive genetic testing in patients at a multidisciplinary inherited heart disease clinic in India from August 2017 to October 2023. It included 77 subjects (48 probands, 29 relatives) with an average age of 43 years, 68% male, and 44% symptomatic, spanning various conditions such as hypertrophic cardiomyopathy, dilated cardiomyopathy, arrhythmogenic cardiomyopathy, peripartum cardiomyopathy, congenital long QT syndrome, Brugada syndrome, and Marfan Syndrome. Next-generation sequencing (NGS) was employed, with a 31% diagnostic yield, 54% identifying variants of uncertain significance (VUS), and 15% being genotype-negative. Genetic testing guided follow-up and treatment, with periodic monitoring recommended for genotype-positive and high-risk VUS carriers, while others were discharged from further surveillance. The study highlights the importance of genetic testing in specialized clinics for effective management and family screening in inherited heart diseases.

Recombinant antibodies (rAbs) offer solutions for improving antigen specificity, enhancing immunogenic potential, and enabling versatile functionalization for disease treatment. Single-chain variable fragments (scFvs) have advanced cancer and viral infection therapies due to their favorable pharmacokinetics and human compatibility. However, experimental antibody selection often requires iterative optimization, prompting a shift toward in silico methods. To streamline this process, rAbDesFlow, an open-source computational workflow, was developed. It integrates antigen selection, antibody library generation, structure modeling, interaction analysis, and consensus ranking to identify optimal rAb candidates for experimental validation. Demonstrated in designing rAbs for ovarian cancer antigen Mucin-16 (CA-125), this workflow provides a blueprint for targeting various disease-specific biomarkers.

Hematopoietic stem cell transplantation can deliver therapeutic proteins to the central nervous system (CNS) through transplant-derived microglia-like cells. However, current conditioning approaches result in low and slow engraftment of transplanted cells in the CNS. Here we optimized a brain conditioning regimen that leads to rapid, robust, and persistent microglia replacement without adverse effects on neurobehavior or hematopoiesis. This regimen combines busulfan myeloablation and six days of Colony-stimulating factor 1 receptor inhibitor PLX3397. Single-cell analyses revealed unappreciated heterogeneity of microglia-like cells with most cells expressing genes characteristic of homeostatic microglia, brain-border-associated macrophages, and unique markers. Cytokine analysis in the CNS showed transient inductions of myeloproliferative and chemoattractant cytokines that help repopulate the microglia niche. Bone marrow transplant of progranulin-deficient mice conditioned with busulfan and PLX3397 restored progranulin in the brain and eyes and normalized brain lipofuscin storage, proteostasis, and lipid metabolism. This study advances our understanding of CNS repopulation by hematopoietic-derived cells and demonstrates its therapeutic potential for treating progranulin-dependent neurodegeneration.