Abstract Background: Hepatocellular carcinoma (LIHC) is a common and aggressive liver malignancy, often diagnosed at advanced stages. Dysregulation of the TP53 tumor suppressor gene critical for cell cycle control, apoptosis, and genomic stabilityis frequently observed in LIHC; however, its prognostic value remains uncertain. Objectives: To investigate TP53 expression levels, prognostic relevance, and molecular interactions in LIHC within a broader pan-cancer context. Methods: Publicly available datasets from TCGA and GEO were analyzed. TP53 differential expression was evaluated using TIMER 2.0, GEPIA, and UALCAN. Survival analysis was performed via Kaplan-Meier Plotter, GEPIA, and UALCAN. Genomic alterations were assessed through cBioPortal. Gene expression validation was conducted using GEO2R and ggplot2. Protein-protein interaction networks were constructed using STRING and GeneMANIA. Results: TP53 mRNA expression was significantly elevated in LIHC tumor tissues compared to normal liver tissues (p < 0.05). Promoter hypo-methylation was noted in tumor samples, potentially contributing to this up-regulation. Survival analysis revealed... Continue Reading

Background: Noonan syndrome (NS) is an autosomal dominant condition characterized by facial dysmorphism, congenital heart disease, growth impairment, and ectodermal findings. Variants in SOS1 account for a large proportion of cases. Case presentation: We report a male infant with nasal bone hypoplasia and shortening of long bones identified during the prenatal period. After birth, he presented with facial dysmorphism, pulmonary valve stenosis, axial hypotonia, and renal anomalies. The karyotype was normal. Whole-exome sequencing with CNV analysis focused on NS-related genes identified a heterozygous SOS1 variant, c.1656G>T (p.Arg552Ser), classified as pathogenic according to ACMG criteria and curated databases, supporting the diagnosis of SOS1-related Noonan syndrome type 4. The SOS1 p.Arg552Ser variant has been reported in individuals with typical NS features, supporting the genotype–phenotype correlation. In this patient, the combination of prenatal skeletal markers and postnatal renal involvement illustrates the wide phenotypic variability. Early molecular confirmation allowed multidisciplinary care and targeted surveillance... Continue Reading

Background: Polydactyly is common congenital limb anomaly characterized by having extra fingers or toes and can be either syndromic or non-syndromic. GLI3 plays an important role in limb development via the Sonic Hedgehog signaling system. Methods and results: In this study, we examined a Pakistan family with postaxial polydactyly in an autosomal dominant manner. Clinical assessment confirmed non-syndromic presentation without further systemic abnormalities. Whole exome sequencing and Sanger validation identified a novel heterozygous missense variant in GLI3 (Glioma-associated oncogene homolog 3) [NM_000168.6: c.3199C>T; p. (Pro1067Ser)].Conclusion: This novel variant expands the GLI3 mutation spectrum and highlights the importance of comprehensive genetic screening for accurate diagnosis and counselling of families with isolated polydactyly. Continue Reading

Genetic disorders remain among the greatest challenges in modern medicine, with over 95% lacking curative therapies. Preimplantation Genetic Testing (PGT) has emerged as a transformative preventive tool, enabling the detection of chromosomal abnormalities (PGT-A) and single-gene disorders (PGT-M) in embryos prior to implantation. At ExpressMed Diagnostics and Research, Bahrain, nearly 700 PGT-A and 25 PGT-M cases have been performed, with a significant impact on reducing miscarriage risk and preventing sickle cell disease transmission. Our data highlight the critical influence of maternal age, with aneuploidy rates rising from ~60% in women under 30 to ~90% in women over 40. In the Gulf region, where consanguinity and genetic disorders are highly prevalent, PGT offers a powerful public health strategy to reduce inherited disease burden, complementing newborn screening and premarital testing. As genomic technologies advance, ensuring accessibility, affordability, and ethical oversight will be essential. PGT represents not only a scientific breakthrough but also... Continue Reading

Background: The BCR::ABL1 gene fusion is the hallmark of chronic myeloid leukemia (CML). Variant Philadelphia chromosome (Ph)-positive cases with complex chromosomal rearrangements involving additional chromosomes occur in 4-11% of c ases, but their prognostic significance remains unclear. Methods: A 20-year-old male presenting with leukocytosis and anemia was evaluated using conventionalcytogenetics, fluorescence in situ hybridization (FISH), and reverse transcription PCR (RT-PCR) to identify chromosomal abnormalities and BCR::ABL1 transcript type. Results: Cytogenetic analysis revealed a novel balanced five-way translocation: 46,XY,t(9;10;15;21;22)(q34;p11.2;q22;q22;q11.2). FISH confirmed the BCR::ABL1 fusion in 97% of nuclei, and RT-PCR detected thee13a2 (p210) BCR::ABL1 transcript. The patient exhibited rapid progression to blast crisis and resistance tofirst-line imatinib therapy. Conclusion: This novel five-way translocation in Ph-positive CML highlights the importance of comprehensivecytogenetic and molecular characterization to detect rare variants that may influence treatment response andprognosis. Continue Reading

Background: Spastic ataxia type 5 (SPAX5) is a rare autosomal recessive neurodegenerative disorder that ischaracterized by a progressive combination of spasticity, cerebellar ataxia, and difficulties with fine motorcoordination. This report aims to highlight the clinical profile, diagnostic findings, and genetic aspects ofSPAX5, emphasizing the value of Whole-exome sequencing in diagnosing rare hereditary disorders. Case Presentation: In this report, we present the clinical progression, findings, and genetic classification of a47-year-old male diagnosed with spastic ataxia type 5, who, over the past decade, has experienced worseningbalance instability, weakness, and increasing walking disturbances. Upon follow-up, he presented with gazepalsy and a noticeable decline in cognitive function. Family history noted a cousin aged 60 with similar symptoms, consistent with the autosomal recessive inheritance pattern characteristic of SCA5. Genetic analysis: Whole exome sequencing (WES) revealed a homozygous likely pathogenic variant in the AFG3L2 gene, confirming the diagnosis of SPAX5. This discovery emphasizes the genetic etiology... Continue Reading