Sleep poses constraints, such as increased vulnerability to predators, that can lead to differences in the use of habitat components across the diel cycle. However, very few studies have systematically evaluated site use of animals across both active and sleep phases. We quantified site use during the active and sleep phases in 412 individuals of eight species (six genera) of agamid lizards, from four habitat types (arboreal, semi-arboreal, rupicolous and ground). Sleep sites differed for five out of the eight species, in all habitat types except rupicolous. Semi-arboreal and arboreal lizards slept on narrower and more compliant perches, likely to detect and avoid predators, whereas ground-dwelling lizards slept in sheltered sites that probably afford a stable thermo-hydric environment. For most species, sleep sites differed from active sites in only a few characteristics, indicating that lizards respond to the potential costs of sleep while being constrained by their morpho-functional abilities. We found equivocal pattens of lower variability of sleep sites compared to active sites, which may be due to low variability in perch options or low costs of sleep in some habitat types. This study provides a large-scale test of diel shifts in habitat use and highlights the need to integrate sleep microhabitat use into ecological and conservation research.
Early pregnancy loss (EPL), particularly when recurrent, represents a profoundly distressing experience for affected couples. Although chromosomal abnormalities are the most common cause of EPL, a substantial proportion of cases, especially those involving euploid embryos, remain unexplained. In this study, we investigated the potential contribution of rare monogenic variants to euploid EPL using whole-exome sequencing (WES). WES was performed on 66 euploid products of conceptions (POCs) from EPLs occurring before 12 gestational weeks. A molecular diagnosis with a high level of confidence, defined as the presence of pathogenic or likely pathogenic (P/LP) variant(s) consistent with the expected mode of inheritance, was established in 13/66 POCs (19.7%). These included one large 21q22.12-q22.3 duplication encompassing DYRK1A and RUNX1. P/LP small variants were detected in CPLANE1, DHCR7, DSG2, DVL1, F5, NF1, RBM8A, SLC6A1, and VWF, representing genes with variable degrees of prior association with developmental phenotypes and, in some cases, limited or no evidence for embryonic lethality. In an additional 9/66 POCs (13.6%), findings were suggestive but not conclusive for a monogenic contribution. These included four cases with compound heterozygosity involving a pathogenic variant and a variant of uncertain significance (VUS) in autosomal recessive genes (GBA1, PAH, PKHD1, and RPGRIP1L), as well as five cases harboring single heterozygous VUS in autosomal dominant genes (MYH3, PRDM6, SCN5A, TBX18, and TSC1). The pathogenic relevance of these variants remains uncertain, particularly in the absence of functional validation. The implicated genes were clustered in biological categories: 1) genes plausibly associated with prenatal or early embryonic lethality, 2) genes causing severe congenital disorders not typically considered embryonically lethal, and 3) genes linked to later-onset or susceptibility phenotypes. These observations are consistent with a spectrum model in which highly deleterious variants may act as primary drivers of embryonic demise, whereas variants with reduced penetrance, later-onset associations or uncertain significance may contribute in a multifactorial context, potentially interacting with additional genetic, maternal or environmental factors. In conclusion, our findings suggest that monogenic variants may contribute to a subset of euploid EPL cases, although the strength of evidence varies considerably across detected variants. The integration of WES into the evaluation of recurrent euploid pregnancy loss holds promise but should be interpreted with caution. Further studies incorporating functional analyses, larger cohorts, and parental data are needed to clarify causality and to define the clinical utility of such approaches in genetic counseling, recurrence-risk assessment, and reproductive planning.
Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction, communication deficits, and restricted, repetitive behaviors. Early and accurate diagnosis is essential for timely intervention and improved outcomes. While numerous efforts have been made to identify reliable biomarkers, no clinically validated protein biomarkers for ASD are currently available. The identification of such biomarkers could aid in diagnosis, subtyping, treatment monitoring, and the discovery of novel therapeutic targets. In this study, we analyzed the serum proteome profiles of children with ASD compared to typically developing children (TDC) using an iTRAQ-based quantitative proteomic approach. Pooled serum samples were assessed to identify potential ASD-associated protein biomarkers. A total of 59 differentially expressed proteins were identified between the ASD and TDC groups. These proteins are implicated in several biological pathways, including cholesterol metabolism, complement and coagulation cascades, tight junctions, regulation of the actin cytoskeleton, and extracellular matrix (ECM)-receptor interactions. Notably, levels of complement C4A, APOC2, and PFN1 were significantly elevated in the ASD group, while proteins involved in ECM-cell interactions - HSPG2, HPSE, and NID1 - were markedly decreased. These findings highlight a distinct proteomic signature in ASD and suggest that the identified proteins may serve as promising candidates for molecular biomarkers. Further validation in larger, independent cohorts is warranted to establish their diagnostic and clinical utility.
Cancer cells rely upon fatty acids (FA) for proliferation, survival, and metastasis. Overexpression of long-chain acyl CoA synthetase 1 (ACSL1), responsible for long-chain FA synthesis, can increase cell invasion and proliferation. Uncoupling protein-2 (UCP2) promotes FA metabolism over glucose utilization in colorectal cancer cells. We aimed to investigate the association of UCP2 45bp ins/del and ACSL1 rs8086 polymorphisms with the clinicopathological characteristics in patients with colorectal cancer. The study included 183 patients with colorectal cancer, 110 (60.1%) men and 73 (39.9%) women, with an average age of 62.1 years. Clinicopathological characteristics: tumor location, histological differentiation, presence of lymph node metastases, presence of distant metastases, and stage of the disease were collected for all patients. Rs8086 polymorphism genotypes were detected by Real-time PCR using TaqMan® SNP Genotyping assay, while genotyping of 45 bp ins/del polymorphism was performed using the PCR method. Distant metastases were more frequent in carriers of the ACSL1 TT genotype than carriers of the CC or CT genotype (p=0.046). Also, carriers of the UCP2 45 I allele (II+ID genotype) had distant metastases more frequently than patients with the DD genotype (p=0.029). It has also been observed that there is a statistically significant association of ACSL1 and UCP2 genotype with cancer localization (p=0.006 and p=0.017, respectively). The results suggest that ACSL1 rs8086 and UCP2 45 bp ins/del polymorphisms are associated with the occurrence of distant metastases and tumor location in patients with colorectal cancer.
Background: Townes-Brocks syndrome (TBS) is a rare autosomal dominant disorder caused by pathogenic variants in SALL1, classically defined by dysplastic ears, anorectal malformations, and thumb anomalies. Renal involvement is a major determinant of prognosis. Results: We report a Serbian family with multiple members with TBS and molecular confirmation of a SALL1 familial nonsense variant (c.1509C>A, p. Tyr503Ter). Detailed phenotypic data were obtained from paediatric and adult medical records. Seven affected patients across three generations exhibited a remarkably consistent renal phenotype characterized by bilateral renal Hypodysplasia and chronic kidney disease (CKD), contrasted by variable extrarenal features. The proband developed CKD progressing to end-stage renal disease (ESRD) in adolescence, requiring kidney transplantation. Her first male cousin (patient 2) presented with anal atresia, dysplastic ears, hypospadias, and congenital hypothyroidism, and currently has stable CKD stage II. Mother of patient 2 has CKD stage III with small hyperechogenic kidneys and proteinuria. The affected grandfather has ESRD and sensorineural hearing loss. Notably, none of the affected individuals fulfilled the complete classical triad of TBS. Conclusion: This family demonstrates intrafamilial phenotypic variability of TBS but with strikingly consistent renal involvement linked to a familial SALL1 variant. TBS should be considered in patients with congenital anomalies of the kidney and Urinary tract (CAKUT) even in the absence of typical limb or anorectal anomalies. Early molecular diagnosis enables appropriate surveillance and timely management of progressive kidney disease.
Kidney transplantation is the best choose of modality for treatment of the patients with end-stage kidney disease (ESKD). However, hereditary conditions like COL4 nephropathy introduce significant obstacles in living kidney donor selection. This review presents a real-world clinical dilemma involving a 24-year-old male with autosomal recessive COL4 nephropathy (Alport syndrome) and his 51-year-old mother, a heterozygous carrier. We analyzed the clinical spectrum of COL4 nephropathy in North Macedonia, where 92 patients have been identified via next-generation sequencing (NGS), and COL4A5 mutations were the most prevalent at 67.4%. Because current the kidney disease improving global outcomes (KDIGO) recommendations for living kidney donor evaluation are general and offer scarce guidance for hereditary conditions, we evaluated the recent 2025 ERK Net/ERA/ESPN criteria. These updated guidelines suggest that while donation is generally avoided in carriers, it may be considered in highly selected individuals over 40 years of age with preserved kidney function and no subclinical kidney damage on biopsy. Careful and individualized evaluation of potential living donors from affected families is essential. This approach is particularly important in settings with persistent organ shortages and limited access to deceased-donor transplantation.
Objective: To define peripheral transcriptomic alterations in newly diagnosed immune thrombocytopenia (ITP) and explore shared disease-associated gene programs with chronic kidney disease (CKD) related autoimmune nephropathies (membranous nephropathy, MN; IgA nephropathy, IgAN). Methods: CD19+ B cells from newly diagnosed ITP patients and healthy controls (n = 4/group) underwent high-throughput sequencing. To complement the limited cohort, six publicly available ITP-related GEO datasets were additionally collected as supplementary transcriptomic resources. Differential expression analyses were performed separately in the dataset and the public datasets using dataset-appropriate workflows, and the intersecting differentially expressed genes were retained as common DEGs for downstream analyses. Functional enrichment was assessed using GSEA, and candidate genes were prioritized using machine-learning approaches, including LASSO, SVM-RFE, and Random Forest, followed by protein-protein interaction (PPI) network analysis. TNF, NLRP3, and IL1B were further validated by qPCR in newly diagnosed ITP patients, remission ITP patients, and healthy controls. CKD, MN and IgAN associated gene sets were curated from GeneCards and OMIM for overlap and PPI analyses. Results: Intersecting the differential expression results from the and public datasets yielded 498 common DEGs, including 243 upregulated and 255 downregulated genes. These genes were enriched in inflammatory and immunometabolic pathways. Machine learning analyses converged on SRGN as a prioritized candidate gene. PPI analysis highlighted inflammatory and immune-related nodes, including TNF and IL1B, while qPCR confirmed increased expression of TNF, NLRP3, and IL1B in newly diagnosed ITP patients, with reduced NLRP3 and IL1B expression in remission. Overlap analyses identified 39 genes shared with CKD, 24 with MN, and 37 with IgAN, with TNF emerging as a recurrent high-connectivity inflammatory node across the overlap derived PPI networks. Conclusions: Newly diagnosed ITP is associated with a distinct inflammatory and immunometabolic B-cell transcriptional program. The recurrent identification of TNF centered and inflammasome-linked signals suggests shared disease associated inflammatory components between ITP and CKD related autoimmune nephropathies. These molecular signatures may contribute to future biomarker development, renal risk stratification, or translational targeting across hematologic and renal autoimmunity.
Aim:This study aims to examine the association between the prevalence of Q192R polymorphism of PON1 gene and the occurrence of atherosclerosis and coronary artery disease in patients in Republic of North Macedonia. Method:This cross-sectional study includes subjects undergoing percutaneous coronary angiography with or without stenting due to monitoring of stable angina or induced ischemia, divided into two groups. Q192R polymorphism and its genotypic variants were analysed. The Polymerase Chain Reaction technique was used as a method for determining the single nucleotide polymorphism. Results:A total of 165 subjects (106 belonging to the coronary artery disease (CAD) group and 59 to non-CAD group were evaluated in terms of their biochemical parameters and genetic variants. Results of the PON1 SNP Q192R groups (QQ, QR and RR) association related to CAD and non-CAD groups, resulted in a non-significant association (p=0.0632, OR=0.511, CI: 0.25-0.595, χ2=3.4508, df=1). In further analyses, to obtain a more precise association, we analysed the association between SNP Q192R groups and stenting patients (control vs. stenting group). Further analysis confirmed the association of QQ vs. QR and control vs. stenting (p=0.0418, OR=0.461, CI: 0.216-0.589, χ2=4.1432, df=1). Conclusion:Results support the concept that genetic variants may contribute to an increased risk of CAD, emphasizing the importance of combined biochemical and genetic testing for better stratification of cardiovascular risk and early confirmation of the predisposition to develop serious cardiovascular disease. Further studies with a larger sample size are needed before Q192R gene polymorphism can be considered as a genetic risk factor for CAD.
Acromesomelic dysplasias (AMDs) are rare skeletal disorders marked by disproportionate shortening of middle and distal limb segments. Among these, AMD Maroteaux type (AMDM), is commonly associated with mutations in NPR2 gene. However, mutations in the Indian Hedgehog (IHH) gene have been linked to several skeletal dysplasia with overlapping features. In the present study, we report a consanguineous Pakistani family presenting with a novel AMDM type skeletal dysplasia that phenotypically resembles but is distinct from AMDM. Mmutational screening was carried out by whole exome sequencing (WES) followed by Sanger sequencing. In silico modeling and molecular dynamics simulation analysis were used to validate the variant. WES identified a novel homozygous missense variant in the IHH gene (c.1018G>A; p. Val340Met) which segregated within the family and was absent in unaffected ethnically matched controls. Structural modelling and simulations indicated that the p. Val340Met substitution destabilizes the IHH C-terminal auto processing domain leading to reduced compactness and stability. These changes are predicted to impair IHH processing and function, thereby contributing to disease onset. This study reports a novel form of AMDM type skeletal dysplasia in a Pakistani family, and identify the novel homozygous IHH variant, thereby expanding the phenotypic and mutational spectrum of IHH-related skeletal disorders.
Background:Biological sex influences immune function and inflammatory regulation, but its molecular role in periodontal disease remains insufficiently understood. This pilot study investigated sex-dependent differences in immune gene expression in patients with severe periodontitis. Methods:Ten systemically healthy, non-smoking adults (five men and five women) with stage III/IV periodontitis were examined. Total RNA was extracted from saliva and analyzed using the nCounter® Human Inflammation Panel (NanoString, Bruker Spatial Biology, USA). Results:Among 249 immune-related genes analyzed, two showed notable preliminary trends of sex-associated differences: AREG was upregulated in males (log2FC = -0.67, d = -1.73, p = 0.03), and NOD2 was elevated in females (log2FC = 1.00, d = 1.36, p = 0.03), although these did not remain statistically significant after FDR correction. Conclusion:These exploratory results suggest hypothesis-generating trends regarding sex-dependent differences in epithelial repair and innate immunity, highlighting AREG and NOD2 as candidate transcripts for further investigation. These initial findings may serve as a foundation for future, larger-scale multicenter studies with sex-stratified designs integrating transcriptomic, hormonal, and epigenetic analyses to clarify how biological sex influences molecular pathways involved in periodontal inflammation.
Background:Secretory breast carcinoma (SBC) is an extremely rare subtype, accounting for ~1% of breast cancers but representing the most common malignant breast tumor in pediatric patients. Although generally indolent, SBC carries a risk of local recurrence even decades after treatment. Its defining molecular hallmark is the ETV6-NTRK3 fusion. Case Presentation:We describe a previously healthy six-year-old girl who presented with a 10 × 10 mm retroareolar breast mass. Histopathology revealed lobular tumor architecture with microcystic, cribriform, and tubular patterns, PAS-positive secretory material, and pronounced mitotic activity. Immunohistochemistry demonstrated positivity for S-100, MUC4, EGFR, and GATA3, with partial ER expression (20%), PR negativity, and HER2 negativity. Due to margin involvement after excisional biopsy, a simple mastectomy with sentinel lymph node biopsy was performed, followed by axillary dissection after six months for suspicious lymph nodes, which proved benign. Genetic Findings:Germline testing (BRCA1/2, TP53, PTEN, CHEK2, PALB2, and others) was negative, excluding hereditary predisposition. Tumor profiling confirmed the canonical in-frame ETV6-NTRK3 fusion (ETV6 exon 5 - NTRK3 exon 13). Therapeutic Implications:The presence of ETV6-NTRK3 not only confirms the diagnosis but also identifies a potential therapeutic target. TRK inhibitors (larotrectinib, entrectinib, repotrectinib) are FDA/EMA-approved for pediatric and adult solid tumors with NTRK fusions and have demonstrated high and durable response rates. Outcome:Six years after surgery, the patient remains disease-free without evidence of recurrence or metastasis. Conclusion:This case highlights the importance of integrating histopathology with molecular profiling in pediatric SBC. The identification of ETV6-NTRK3 provides diagnostic specificity and offers a precision oncology option in the event of relapse. Long-term surveillance and multidisciplinary follow-up remain essential for optimal care.
Syndromic X-linked intellectual disability associated with pathogenic variants in HUWE1 includes moderate to severe intellectual disability, dysmorphic features, and epilepsy, and is characterized by clinical variability, especially among carrier females. We present three unrelated symptomatic patients with severe neurodevelopmental symptoms and dysmorphic features, in whom molecular variants c.12469C>G, p.(Leu4157Val); c.5520+4_5520+7del, p.?; and c.4128G>A, p.(Met1376Ile) in the HUWE1 gene were identified. Their phenotypic presentations were consistent with previously reported cases of pathogenic HUWE1 variants. X-chromosome inactivation analysis in blood DNA revealed highly skewed inactivation (97:3) in a female patient, which may help explain the symptomatic course of the disease in her. De novo HUWE1 pathogenic variants in females are frequently associated with a full-blown phenotype. In familial cases, carrier females may be asymptomatic or present mild cognitive impairment, while affected males often exhibit a more severe clinical course. Skewed X-chromosome inactivation may contribute to disease manifestation in female carriers.
Cleidocranial dysplasia is a rare autosomal dominant skeletal dysplasia. We present the first case in the literature involving a deletion of the 3 ' UTR of RUNX2 gene associated with a cleidocranial dysplasia spectrum disorder, along with the diagnostic odyssey that preceded the establishment of this diagnosis. We describe a female patient with a classical phenotype of cleidocranial dysplasia, followed by a clinical geneticist since the neonatal period. Whole genome sequencing revealed a suspected deletion encompassing the 3 ' UTR of RUNX2 gene, initially classified as a variant of uncertain significance. This deletion was subsequently confirmed using a custom-designed qPCR assay and reclassified as likely pathogenic, thus considered causative for the disease. The diagnosis of cleidocranial dysplasia due to RUNX2 gene dysfunction is supported by a clear phenotype-genotype correlation, the de novo origin of the variant, and functional studies underscoring the importance of the 3 ' UTR for RUNX2 gene function. Our case report provides new evidence supporting the functional significance of the 3 ' UTR of RUNX2 gene, whose haploinsufficiency, due to a small novel deletion of 4.2 kb, results in the classical phenotype of cleidocranial dysplasia. As well, our case illustrates that whole genome sequencing is advantageous for detecting copy number variants.
Gastric cancer is a multifactorial malignancy influenced by genetic and environmental factors. Cholecystectomy may lead to bile reflux, causing potential gastric mucosal injury. hTERT and c-MYC are key regulators in cellular proliferation and oncogenesis. Although epidemiological data generally indicate no strong association between cholecystectomy and gastric cancer, existing studies are limited and confounded by other risk factors. This study aimed to investigate the contribution of bile acid exposure post-cholecystectomy to gastric cancer development and to evaluate hTERT and c-MYC expressions. A total of 100 participants were enrolled at Manisa Celal Bayar University Hospital (September 2021-May 2023), categorized into gastric cancer (n=32), cholecystectomy (n=34), and control groups (n=34). Demographic data, Helicobacter pylori status, intestinal metaplasia presence, and gene expression levels were analyzed. Ethical approval and informed consent were obtained. Gene expression was assessed from endoscopic biopsy samples. Mean ages were higher in the cancer group (p<0.05). Female predominance was observed in the cholecystectomy group (p=0.021). No significant differences were found regarding H. pylori infection, intestinal metaplasia, or gene expressions related to metastasis. However, c-MYC and hTERT expressions were significantly lower in the cholecystectomy group compared to cancer and control groups (p<0.001). Female participants exhibited consistently lower gene expression levels than males (p<0.05). Although cholecystectomy was not directly linked to increased gastric cancer risk, it may contribute in genetically susceptible individuals. Reduced c-MYC and hTERT expressions suggest a potential role in future cancer risk stratification.
Variation in aspects of carotenoid-based coloration reflects physiological health in many taxa. Painted turtles (Chrysemys picta) have brightly colored limb stripes produced by carotenoids, but the function of this color and its relation to physiological function are unknown. We tested the hypothesis that variation in painted turtle forelimb stripe coloration is associated with variation in physiological health – including glucocorticoids and both innate and adaptive immune function. We assessed adult painted turtles of both sexes across a range of sizes/ages from a long-studied population. We found that body size – a strong indicator of age in this species – was associated with changes in forelimb stripe color, such that larger turtles have brighter, more colorful stripes with increased contrast from the background forelimb color. We further found that a number of physiological health measures either changed with size, or differed between sexes, yet physiology measures were not associated with stripe color. Thus, forelimb stripe coloration is not a direct honest signal of quality. Secondarily, we provide a suite of protocols for future use to understand physiological variation of reptiles in the wild. We discuss our results in the context of signaling, physiological health, aging, and sex-specific life histories. Carotenoid-based coloration is an honest signal of quality in many vertebrates, and many studies have detected relationships between physiological state and coloration of ornaments used to communicate with conspecifics. However, the relationships between coloration and physiological fitness in many non-avian vertebrates remain untested, and studies that assess a suite of physiological measures including stress levels and immune function are rare. We assessed relationships among measures of physiology, size (age), sex, and forelimb stripe color in the colorful painted turtle. We found that stress response measures and immune function were not associated with forelimb coloration. Instead, brightness and hue increased with increasing body size. This study provides the foundation for future work to assess whether painted turtle color is a signal of health to conspecifics, and whether such coloration plays a role in painted turtle fitness.
The purpose of our study is to expedite cancer diagnosis through the development of software for rapid detection of hereditary breast cancer (BC) with negative BRCA1/2 on MATLAB, utilizing a fuzzy logic system with several variants of genes associated with BC. This system serves as a clinical decision-support tool, assisting in early classification and interpretation of genetic variants by combining clinical and genetic data. Clinical data were obtained from Erciyes University Faculty of Medicine Department of Medical Genetics and Uludağ University Faculty of Medicine Department of Medical Genetics. 488 individuals were studied. Only 90 of them were relevant to our investigation since their BRCA1/2 genes did not exhibit notable genetic mutations. We examined 16 distinct breast cancer risk factors and focused on mutations related to 18 hereditary BC genes. The collected data were integrated into the developed system, and various membership functions were given varying degrees of possibility, ranging from 0 to 1, depending on their participation in input clusters. After the system was trained on 90 cases and validated on six independent patients, its accuracy was assessed, yielding reliable results. Following the training phase, outcomes revealed the presence of two pathogenic variants at 0.92 (92%), two benign variants at 0.25 (25%), and two variants of unknown significance at 0.5 (50%). Given the high incidence of breast cancer, early prediction is paramount. Despite the emergence of fuzzy logic systems in medical applications, limited research akin to our study exists. The establishment of this artificial intelligence software holds promise for advancing the early detection of BC in future clinical applications.
Introduction:A group of primary bone tumors called chondrosarcomas are diverse and characterized by neoplastic tissue of hyaline cartilage. They are the second most typical primary osseous cancer. Recurrence is indicative of a poor prognosis because traditional chondrosarcomas are resistant to treatment. Our knowledge of the pathobiology of conventional chondrosarcomas has greatly expanded owing to recent findings in these tumors' biology, genetics, and epigenetics studies. These findings also provide information on possible treatment targets. CHEK2 encodes a checkpoint kinase involved in DNA damage response and cell cycle regulation, and it is an important cancer susceptibility gene. Methods:The Gene2 drug and DSEA assisted with in silico screening. The antitumor activities of the candidate drugs were extracted from DepMap via the PRISM viability assay on eight chondrosarcoma cell lines. Results and Conclusion:Advances in studies show promise for discovering potential targeted treatments for cancer. Bisacodyl is a targeted G protein-coupled receptor 35. G protein-coupled receptors are widely known targets for cancer treatment. Here, we showed that bisacodyl can be a potential therapeutic agent in chondrosarcoma cell lines.
Background:Reciprocal translocations are one of the most common structural chromosomal rearrangements in humans, they are due to the exchange of chromosome material between two nonhomologous chromosomes.If a person carries a balanced reciprocal translocation, meiosis may produce normal gametes, as well as gametes with either balanced or unbalanced abnormalities, depending on the segregation pattern during gametogenesis. All types of segregations can occur, although with different percentages. The adjacent-2 segregation is the less common one and it often leads to non-viable products in many species. Case presentation:We report a case of an 18 months-old female patient, who was referred to the medical genetics' consultation for psychomotor retardation and facial dysmorphism. A postnatal constitutional karyotype was performed in our laboratory on a peripheral blood sample followed by a parental karyotype. The results revealed an additional derivative chromosome 9 in the patient resulting from an adjacent-2 segregation in the mother. Conclusion:This observation highlights the possible occurrence of rare mechanisms of segregation during meiosis in families with a reciprocal translocation. Investigating these events is crucial for both diagnosis and genetic counseling.
X-linked adrenoleukodystrophy (X-ALD) is a fatal neurodegenerative disorder caused by mutations in the adenosine triphosphate-binding cassette D1 (ABCD1) gene. In this study, we report the case of a Moroccan patient diagnosed with X-ALD due to a mutation in the ABCD1 gene. This diagnosis enabled a genetic counseling with presymptomatic analysis of the disease in the patient's brother, facilitating proactive management for the family. This work expands the clinical and genetic spectrum of XALD and underscores the critical role of presymptomatic testing in the management of neurodegenerative diseases.
Objective:Colorectal cancer is the third most common malignancy in the world and among the most frequent causes of cancer-related death. Our study aimed to evaluate the molecular profile of the patients diagnosed with colorectal carcinoma at Clinical Hospital Acibadem-Sistina in Skopje. Materials and methods:This study is retrospective-prospective, conducted at the Department of histopathology and cytology, at Clinical Hospital Acibadem-Sistina in Skopje. Tissue samples from surgical material from 152 patients diagnosed with CRC were processed for molecular and immunohistochemical analysis. KRAS and BRAF mutations were analyzed, and MMR status was obtained. In 90 metastatic cases, evaluation of HER2 and PDL-1 expression was performed on a tissue microarray. Results:Among 152 analyzed patients diagnosed with colorectal carcinoma, the majority were males (98, 64.47%) compared to females (54, 35.53%). The mean age was 68.4±11.3 years; the median age was 70 years. KRAS/NRAS mutations were detected in 47(31%) of patients, BRAF mutations in 11(7%) patients, and mismatch repair gene deficiency (MMRd) was found in 15(10%) of patients. HER2 positive expression was present in 36(40%) of patients, and 17(19%) of patients showed PDL-1 expression. In the group of 17 PDL1-positive tumors, a cutoff of more than 1% positive tumor cells was detected in 10 cases, more than 10% tumor cells in 4 cases, and more than 50% tumor cells in 3 cases. From 36 HER2 positive cases, 32(32,5%) were with score 2+, and 4(4,4%) with score 3+. Conclusions:Continued research into molecular mechanisms and biomarkers holds the promise of further improving CRC outcomes through personalized and effective interventions.
