We present a case of a 5-year-old, who developed refractory, multifocal myoclonus, which progressed over several weeks, leading to a profound functional decline. The diagnostic workup was complicated by a compelling genetic finding that suggested a possible primary epileptic encephalopathy. However, meticulous history-taking uncovered key details inconsistent with a purely genetic disorder, raising suspicion for an alternative, acquired condition. This case highlights the critical importance of a detailed clinical history and neurologic examination to guide the diagnostic process, particularly when a patient's evolving story does not fully align with initial genetic testing.

ABSTRACT Background This subgroup analysis investigates the clinical characteristics, treatment patterns, and outcomes of chronic lymphocytic leukemia (CLL) in the Middle East (ME). Research design and methods Retrospective study retrieved medical records of CLL patients treated for ≥12 months (CLL-treated) or treatment-naïve (TN). Results included data from 442 CLL-treated and 123 TN patients across five ME countries. Results CLL-treated group mean age: 61.1 ± 11.28 years; TN cohort: 63.5 ± 13.53 years. Most patients in both groups were male. CLL-IPI scores were mostly unavailable in both cohorts. Cytogenetic abnormalities were tested in 20.6% of CLL-treated and 18.7% of TN cohorts, with del(17p) being the most common abnormality (12.4% and 11.4%, respectively). TP53 aberrations were found in 9.0% of CLL-treated and 9.8% of TN cohorts. Regarding first-line treatment, 76.5% received CIT, while 17.9% received targeted therapies, with ibrutinib (75.9%) being the most common. CIT use led to significant resource utilization, including outpatient visits, length of stay, and blood transfusions. Conclusion CLL management in the ME is characterized by suboptimal utilization of risk-based treatment and genetic testing despite access to targeted therapy. Poor CLL outcomes stem from reliance on CIT, associated with an unfavorable safety profile and healthcare resource use compared to targeted therapies in the region. Clinical trial registration www.clinicaltrials.gov identifier is NCT04964908.

The rapid advancement of science and technology, particularly in forensic science, has significantly enhanced crime investigation methodologies. One such advancement is the utilization of Scientific Crime Investigation methods, specifically the analysis of touch DNA from fingerprints. This research investigates the efficiency of fingerprint powders and swabbing agents in improving the quality and quantity of touch DNA for forensic applications. Touch DNA, derived from cellular materials like sweat and skin cells, presents a valuable source of genetic material for identification purposes. The study involved experimental analyses using Regular Silk Black Fingerprint Powder and Magnetic Dual-Purpose Powder, coupled with non-ionic detergent surfactants as swabbing agents. DNA samples were collected from volunteers with varying DNA shedding levels, processed, and analyzed using quantitative PCR and capillary electrophoresis. Results indicated that fingerprint powders significantly reduce the quantity and quality o

Quantification of plasma APOE4 with a novel automated Lumipulse immunoassay enables the identification of homozygous and heterozygous APOE ε4 carrier status.

Our previous study demonstrated that training oncologists to provide genetic counselling for ovarian cancer patients in Malaysia, an upper-middle-income Asian country, increased uptake of genetic testing to 80% when the test was free under research. However, in practice, genetic tests are unlikely to be provided for free in low-and-middle-income countries. In this study, we explored the willingness to pay (WTP) for genetic testing among ovarian cancer patients in Malaysia. In this multi-center study, ovarian patients without prior genetic counselling were administered questionnaires on WTP (a contingent valuation exercise), facilitators and barriers to genetic counselling, and followed up for at least 6 months. We estimated the WTP value and explored factors associated with being willing to pay using logistic regression. Of 100 sequential patients recruited, 58% stated WTP for genetic testing at median of MYR1,000 (interquartile range=MYR1,125). Older participants were less likely to be willing to pay (odds ratio=0.95; 95% confidence interval=0.91-0.99). Reasons for being unwilling to pay included affordability (71%), belief that it should be paid by government or insurance (19%) and preference not to know their genetic status (14%). At the end of follow-up (mean 5±17 months), 17% took the test at full price. In this exploratory study, stated WTP for genetic testing was high but only at a reduced price. At follow-up, only a minority of patients paid the full price. A co-payment framework or subsidy scheme may be needed to reduce the significant cost barriers to genetic testing in Malaysia.

Increased yield of genetic diagnoses in inherited heart diseases using expanded genome and RNA-splicing analyses.

Germline Variants in Indian Non-Small Cell Lung Cancer Patients With Familial Aggregation: A Prospective Cohort Study.

Screening rare genetic diagnoses for amenability to bespoke antisense oligonucleotide therapy development: A retrospective cohort study.

Using Genetics for Glaucoma Screening and Risk Stratification: The LXXXII Edward Jackson Memorial Lecture.

Alagille Syndrome (ALGS) is a rare multisystem disorder of autosomal dominant type which is primarily caused due to mutations in the JAG1 gene and, less commonly, NOTCH2, both integral to Notch signalling. Clinically, ALGS is further characterised by cholestatic liver disease because of intrahepatic bile duct paucity, along with some cardiac and skeletal abnormalities, ocular defects, renal involvement, and distinct facial features. Diagnosis of ALGS depends upon the presence of at least three of five main clinical features, which are later supported through liver biopsy, genetic testing, and imaging. Differential diagnosis of ALGS includes biliary atresia, Progressive Familial Intrahepatic Cholestasis (PFIC), neonatal hepatitis, and syndromes with overlapping phenotypes such as Noonan and Kabuki syndromes. Management in such cases is largely supportive, which mainly focuses on relieving cholestasis and pruritus, along with proper nutritional adequacy, and addressing systemic complications. Liver transplant is reserved only for end-stage disease or intractable symptoms. A multidisciplinary approach is an essential aspect of treatment to improve patient outcomes, along with quality of life.

To report a case of Fabry disease (FD) in a female patient with a novel heterozygous deletion in the galactosidase A (GLA) gene. A 35-year-old woman with a prior diagnosis of FD confirmed by genetic testing presented with eye irritation, progressive vision loss, and systemic symptoms. Comprehensive ophthalmologic evaluation included slit-lamp biomicroscopy, fundoscopy, visual field testing, optical coherence tomography (OCT), and OCT angiography (OCTA) of both posterior and anterior segments was performed. Bilateral corneal verticillata was observed on slit-lamp examination. OCT and OCTA of the macula revealed intact retinal structures. Despite normal conjunctival and episcleral vessels on clinical examination, anterior segment OCTA showed mild conjunctival vessel tortuosity. Genetic testing of blood sample identified a novel heterozygous deletion frameshift mutation in the GLA gene (c.816delC, p.Phe273LeufsTer9). Systemic evaluations confirmed multiorgan involvement, including hypertension, renal microalbuminuria, cardiac abnormalities, pulmonary dysfunction, and hyperprolactinemia. Corneal verticillata is a hallmark ocular finding in FD. Anterior segment OCTA can reveal subtle vascular abnormalities not detectable through routine examination. The identification of a novel GLA likely pathogenic variant expands the genetic spectrum of FD.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare neurodegenerative condition that rapidly progresses with language regression, loss of ambulation, blindness, intractable seizures, and premature death in childhood. Enzyme replacement therapy has transformed the clinical trajectory of CLN2 disease, and early genetic testing is crucial because enzyme replacement therapy cannot reverse clinical progression. Lack of clinician awareness of early clinical symptomatology, initially normal language development, and history of provoked or treatment-responsive seizures may contribute to diagnostic and treatments delays. There remain challenges in equitable enzyme replacement therapy access globally and implementation of dual treatment to address retinopathy. There is a need to better understand the phenotype of CLN2 disease in the era of enzyme replacement therapy, including children who receive treatment presymptomatically. Gene therapy is a promising curative treatment, notwithstanding the mixed clinical evidence on efficacy and challenges achieving widespread brain transgene expression. This review explores our current understanding of early clinical presentation of CLN2 disease, epilepsy phenotype, role of genetic testing, novel biomarkers, and precision treatments including enzyme replacement therapy.

Sialic acid-Retaled disorders: Advances in pathophysiology, diagnostic challenges, and differentiating mimics.

This review aims to explore the relationship between autoinflammatory diseases (AIDs) and vasculitis, with a focus on recently identified syndromes and newly published data since 2016. While the connection between innate immune dysregulation and systemic inflammation is well established in AIDs, the occurrence of vasculitis in these disorders remains underrecognized and often misclassified.We discuss vasculitic manifestations in a wide range of AIDs, including familial Mediterranean fever, DADA2, HA20, VEXAS, CAPS, TRAPS, HIDS/MKD, Blau syndrome, and others. Each condition presents a unique pattern of vascular involvement, ranging from incidental cutaneous findings to life-threatening systemic vasculitis. The underlying mechanisms often involve overactivation of inflammatory pathways such as IL-1β, or NF-κB, and in some cases, novel genetic mutations affecting non-inflammatory pathways such as purine metabolism. The histologic, clinical, and genetic features often differ from classic vasculitic syndromes. Recognizing vasculitis in the context of AIDs is critical for early diagnosis, especially in pediatric patients or those with treatment-resistant or atypical presentations. Genetic testing should be considered in such cases. Understanding these distinct disease patterns allows physicians to tailor management strategies, including biologic therapies or hematopoietic stem cell transplantation, improving outcomes in these complex and often severe disorders.

Effect of presentation formats for direct-to-consumer genetic testing results: A web-based experimental study in South Korea.

Thalassemia is mainly prevalent in southern China, but consistent regional epidemiological data remain scarce in Hubei Province (central China). The present study characterized thalassemia genotypes and hematological parameters in 2,604 non-selectively screened individuals of reproductive-age (mean age, 31.39±5.72 years) and 407 pediatric subjects (mean age, 3.19±4.31 years) with clinical indications enrolled at Renmin Hospital of Wuhan University (Wuhan, Hubei), from January 2019 to September 2024. Peripheral blood and serum samples were analyzed for red blood cell count (RBC), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), serum iron, total iron binding capacity, serum ferritin (SF), folate, transferrin saturation and vitamin B12 (VITB12) levels. Genetic testing was performed using gap-polymerase chain reaction (gap-PCR), reverse dot blot, Sanger sequencing and research-grade gap-PCR. The overall thalassemia carrier rates were 14.94% (reproductive-age group), 37.35% (pediatric group), and 17.97% (combined). Common α-thalassemia genotypes included--SEA/αα and -α3.7/αα, and dominant β-thalassemia mutations were β654, β41-42 and β17, aligning with neighboring provinces, differing from southern high-prevalence regions. Most phenotypes exhibited reduced RBC, Hb, MCV, MCH (all P<0.01) and elevated SF, VITB12. The high pediatric carrier rate may stem from selection bias due to clinical enrollment criteria. Notably, Hb and MCH were effective screening markers. In conclusion, Hubei has a substantial thalassemia burden (especially in children), and enhanced prenatal screening/counseling is urgently needed.

Genetics of Thoracic and Thoracoabdominal Aortic Dissections and Aneurysms.

Genetic Risk Stratification in Arrhythmogenic Left Ventricular Cardiomyopathy.

DNA alloys: The enduring story of touch DNA on metals.

Droplet digital PCR (ddPCR) allows highly sensitive detection of minimal amounts of a target of interest. The most common applications of ddPCR have traditionally been detection of genetic variants, copy number variations and gene expression, but the method has great potential also for DNA methylation analyses. We here describe an optimized and standardized protocol for methylation-specific ddPCR analyses, including use of an internal control; the 4Plex, and an automated algorithm for scoring of positive droplets; PoDCall. We also describe a protocol for bisulfite treatment using either of two kits from QIAGEN, utilizing cell-free DNA (cfDNA) or tissue samples as staring material. Implementation of these protocols across laboratories could contribute to more robust and consistent ddPCR methylation results.