Balkan Journal of Medical Genetics Feed

Results Of PMP22 Gene Deletion and Duplication Analysis in 100 Patients with Hereditary Neuropathy

Wed, 14 Oct 2026 00:00:00 GMT

BACKGROUNDHereditary neuropathies, including CMT1A and HNPP, are commonly associated with PMP22 gene dosage alterations. Although MLPA is widely used, cost-effective alternatives are still needed in resource-limited settings.METHODSWe analyzed PMP22 gene deletions and duplications in 100 patients with suspected hereditary neuropathy using PCR-RFLP.RESULTSPMP22 deletions and duplications were detected in 18% and 8% of patients, respectively.CONCLUSIONSOur findings support PCR-RFLP as a practical and accessible screening method for PMP22 gene dosage abnormalities, particularly in settings where advanced molecular techniques are not readily available.

Long-Term Kidney and Patient Survival after Deceased Donor Transplantation in Two Brothers with Alport Syndrome from the Same Donor

Wed, 14 Oct 2026 00:00:00 GMT

Alport syndrome is a hereditary disorder caused by a mutation in type IV collagen, leading to progressive kidney disease and eventual end- stage renal failure. Kidney transplantation represents the optimal therapeutic option, typically associated with excellent graft survival. We report a long-term outcome in two brothers with genetically confirmed Alport syndrome (COL4A5 mutation inherited from their mother, also on hemodialysis). Receiving kidneys from the same deceased donor with only one HLA mismatch. A standard immunosuppression therapy was administered, including Anti-Thymocyte Globulin (ATG) as an induction, followed by maintenance therapy (steroids, a calcineurin inhibitor, and mycophenolic acid). Graft function in both recipients was established immediately, with diuresis up to 8 L and normalized serum creatinine within the first 24 hours after transplantation. During 12 years of follow-up, graft function remained stable, with normal serum creatinine levels, no occurrence of proteinuria, and no development of anti-HLA antibodies. The younger brother developed gingival hyperplasia and steroid-induced diabetes as complications of the therapy. Both patients remain employed and have families.

Association between Tacrolimus Variability and ABCB1/CYP3A5 Genetic Polymorphisms in Kidney Transplant Recipients

Wed, 14 Oct 2026 00:00:00 GMT

The aim of this study was to assess tacrolimus variability in kidney transplanted patients and its associations with genetic polymorphisms in CYP3A5(rs776746) and ABCB1(rs1045642) in North Macedonia. We conducted an observational study including 84 kidney transplant recipients who met inclusion criteria. Variability of tacrolimus was evaluated using the concentration-to-dose ratio (C0/D) and coefficient of variation (CV%). Single-nucleotide polymorphisms (SNPs) were identified using real-time polymerase chain reaction. Among the 84 patients, males predominated (70%), with a mean age of 37.57years. Analysis for variability revealed C0/D<1.05ng/ml/mg in 15% and CV>30% in 17% examined population. The majority of patients (86%) had the CYP3A5 GG genotype, whereas 14% carried at least one expresser allele (CYP3A5 AA/AG). Regarding ABCB1, 26% of patients had the CC genotype, 46% CT, and 27% TT. Patients carrying the CYP3A5 expresser genotype (AA/AG) demonstrated a significantly higher risk of low C0/D ratio (<1.05 ng/mL/mg) compared to non-expressers (58% vs. 8%; OR = 2.01; 95% CI: 1.114–3.624; p = 0.001). Additionally, expresser patients required significantly higher daily doses of tacrolimus to achieve target blood concentrations compared to non-expressers (5.11 ± 2.21 mg vs. 3.21 ± 1.78 mg, p = 0.014). No significant association was found between ABCB1 polymorphisms and tacrolimus variability parameters. This is first study in our country that explores and verifies the association between variability of tacrolimus and genetic polymorphisms in kidney transplant recipients. Our work advances the effort to tailor more personalized treatment, minimizing negative outcomes and adverse effects to the lowest achievable level.

Partial Trisomy 20qter on a Derivative Chromosome 22 in a Northern Italian Genetic Isolate with Oculo-Auriculo-Vertebral Spectrum-Related Features

Wed, 14 Oct 2026 00:00:00 GMT

Duplications of distal 20q are uncommon and the connection to oculo-auriculo-vertebral spectrum (OAVS) is still not clear. In this paper we describe a family-based cytogenetic case of a geographically isolated community in Northern Italy. Clinical data, pedigree information, and cytogenetic report from the proband were collected. Relatives were examined for OAVS-related features. Subtelomeric FISH analysis was performed with probes for 20qter and D22S1726 using peripheral blood lymphocytes to assess the rearrangement in detail. Descriptive statistics with 95% confidence intervals were computed. FISH demonstrated additional terminal material on der (22) consistent with a complex subtelomeric rearrangement and partial trisomy of 20qter. Among the 30 evaluated relatives, 15 (50.0%; exact 95% CI, 31.3–68.7) carried the rearrangement. Of these, 5 (33.3%; exact 95% CI, 11.8–61.6) exhibited features within the oculo-auriculo-vertebral spectrum, including preauricular tags, microtia or aural atresia, hemi-facial microsomia, ocular anomalies, vertebral defects, congenital heart disease, and hearing impairment. FISH does not provide information about the duplication segment or genes involved; therefore, MYT1 inclusion into the duplication cannot be confirmed and requires further chromosomal microarray, SNP-array, MLPA or genome sequencing analysis. In this pedigree, the findings support the distal 20qter/20q13.33 as a possible candidate genomic region associated with OAVS-related features and support high-resolution genomic studies and genetic counselling in affected families.

Application of Fluorescence in situ Hybridization in Malignant Hemopathies: First Experience from Albania

Wed, 14 Oct 2026 00:00:00 GMT

Introduction:Genetic alterations in genome organization are essential for the clinical evaluation of hematological disorders. Fluorescence in situ hybridization (FISH) enables the detection and determination of the frequency of genetic abnormalities.Objectives:This study aims to apply selected probes as a diagnostic approach to aid in establishing diagnosis, predicting prognosis, and monitoring disease progression.Results:Fluorescence microscopy analysis of inter-phase cells was undertaken at the Laboratory of Molecular Cytogenetics, within the Clinical Genetics Laboratory Service, in a cohort of 330 adult patients with hematological disorders clinically established by the Hematology Service at QSU “Mother Teresa,” Tirana, Albania.Detection of the BCR-ABL1 genetic rearrangement was observed in 50 (40%) patients with CML, providing assistance in establishing a rapid diagnosis and monitoring patient response to the treatment provided. Among AML patients with the PML-RARA genetic rearrangement, 11 (25%) achieved complete remission in a short period following targeted therapy, resulting in a reduced risk of mortality.The deletion of TP53 gene identified in a group of 44 (50%) CLL patients represents a major clinical challenge due to its association with a poor prognosis, resistance to the given treatment and an aggressive disease with frequent relapses.Conclusions:Through the identification of specific genetic mutations, molecular cytogenetics contributes to early diagnosis, improving the prognosis and choosing the most appropriate treatments, significantly improving the survival and quality of patient’s life.

DNA Methylation and TMPRSS2-ERG Fusion Status in Patients with Prostate Cancer from The Republic of North Macedonia

Wed, 14 Oct 2026 00:00:00 GMT

Prostate cancer is the second leading cause of male deaths in the Western world and the most commonly detected cancer in males. Recent studies have pointed out that DNA methylation and TMPRSS2-ERG fusion transcript, have a high presence among prostate tumor cells. It is estimated that these two molecular mechanisms could be used as potential markers for early detection of malignancy, and/or progression of prostate cancer disease.The study aimed to test the presence of the DNA methylation and TMPRSS2-ERG fusion transcript in patients with prostate cancer, as a baseline database for further genetic examination. This prospective clinical study focused on a random sample of 88 patients with prostate carcinoma. For the detection of methylation status in 26 tumor suppressor genes (TP73, CASP8, VHL, RARB, MLH1, RASSF1, FHIT, APC, SLC9A2-2, ESR1, CDKN2A, CDKN2B, DAPK1, KLLN, PTEN, CD44, GSTP1, ATM, CADM1, CDKN1B, CHFR, BRCA2, CDH13, HIC1, BRCA1 and TIMP3), in CaP patients the Multiplex Ligation-Dependent Probe Amplification (MLPA) analyses was performed. All samples were conducted on a Real-time PCR analysis for the detection of the TMPRSS2-ERG fusion transcript. Additionally, the data from the histopathology results of tissues, and level of prostate-specific antigen (PSA) in blood were used.Genome-wide DNA methylation profiles were detected in 10 out of 26 genes: GSTP1was found in 53,4 % of samples, RARB in 44,32%, RASSF1 in 63,6%, APC in 42%, CDH13 in 39,7%, CASP8 in 25%, CD44-12,5%, TIMP3-2%, ESR1-9% and CADM1-1%. Cohen’s (κ) fair agreement test has shown a linear positive moderate correlation between PSA level and 4 genes (RARB, APC, GSTP1, and CDH13), and a significant linear positive moderate correlation between Gleason Score and 9 methylated genes (GSTP1, RARB, RASSF1, APC, CDH13, CASP8, IMP3, ESR1, and CADM1), except for gene CD44. TMPRSS2-ERG fused transcript was detected in 32 out of 88 (36,4%) of the samples. There were no significant differences between patients with/without detected TMPRSS2-ERG fusion related to Gleason score and PSA level. In conclusion, additional studies need to be performed in appropriately powered clinical cohorts that will define the positive diagnostic meaning of TMPRSS2-ERG fusion transcript, point to the sites in the genome that are under the influence of DNA methylation, in that manner offering additional information for further management of the CaP disease.

Rare Double Reciprocal Translocations in a Man with Reproductive Success and Recurrent Pregnancy Loss

Wed, 14 Oct 2026 00:00:00 GMT

Double reciprocal translocations represent an extremely rare cytogenetic entity. Carriers have a significantly increased risk of producing unbalanced gametes during meiosis, which can lead to adverse reproductive outcomes such as miscarriages or offspring with congenital anomalies. Despite the high reproductive risk, they can give birth either to a balanced translocation carrier with a normal phenotype (similar to the parents) or to a chromosomally normal completely healthy infant, resulting only from alternate 2:2 segregation. Here, we report an exceptional case of double-balanced reciprocal translocations involving four chromosomes (1, 3, 15 and 18) in a phenotypically normal male partner. The couple was investigated due to a history of recurrent pregnancy loss, having already had one phenotypically normal child. The aim of this report is to analyze the cytogenetic finding, predict the possible meiotic segregation outcomes, and discuss the implications in genetic counseling.

Plasma Microrna Profiling in Overweight and Obese Pregnant Women: An Exploratory Pooled-Sample Study

Wed, 14 Oct 2026 00:00:00 GMT

Background: Maternal overweight and obesity are associated with metabolic, vascular, and obstetric complications. Circulating microRNAs (miRNAs) are stable in plasma and may reflect obesity-related molecular alterations during pregnancy. Aim: To compare plasma miRNA expression profiles between normal-weight and overweight/obese pregnant women. Methods: The study included 50 pregnant women: 25 with normal weight and 25 with overweight/obesity. RNA was isolated from individual plasma samples and combined into one pooled RNA sample per study group. The pooled samples were analyzed in technical triplicate using a 96-well miRCURY LNA PCR panel containing 84 target miRNA assays and quality-control/reference assays. Results: Seventeen target miRNAs met the predefined >2-fold higher-expression threshold and 15 met the <0.5-fold threshold in the over-weight/obese pool. miR-21-5p was the only target miRNA that met both the predefined twofold magnitude criterion and the nominal p < 0.05 threshold (fold change = 2.58; p = 0.030266). Conclusion: The pooled-sample analysis identifies miR-21-5p as an exploratory candidate signal associated with maternal overweight/obesity. Individual-sample testing and validation in larger independent cohorts are required before biomarker performance or clinical utility can be established.

First Case of H Syndrome in Northern Morocco: Clinical Features and Literature Overview

Wed, 14 Oct 2026 00:00:00 GMT

H syndrome is a rare multisystem genodermatosis with an autosomal recessive inheritance, characterized by cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, short stature, hyperglycemia, hallux valgus and flexion contractures of fingers and toes. To date, 161 cases have been reported worldwide with limited data from North Africa. Herein, we report the case of a 17-year-old Moroccan girl diagnosed with H syndrome on the basis of clinical features and molecular testing. Clinical examination revealed dysmorphic features with insulin-dependent diabetes, sensorineural hearing loss, short stature, and progressive hyperpigmented indurated skin lesions with hypertrichosis predominantly affecting the thighs and genital region, associated with flexion contractures of the fingers and toes. Genetic testing identified a homozygous pathogenic splice-site variant c.300+1G>C in the SLC29A3 gene, previously reported to be associated with H syndrome. This is the first report of this mutation from northern Morocco, highlighting regional prevalence, phenotypic variability and the challenges faced in diagnosis due to high cost and limited access to molecular testing.

Progressive Supranuclear Palsy-Primary Lateral Sclerosis Overlap Syndrome in a Patient with a CYLD Variant

Wed, 14 Oct 2026 00:00:00 GMT

Objective:Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome characterized by progressive axial rigidity, vertical gaze palsy, dysarthria, and dysphagia. This report describes a case of PSP-primary lateral sclerosis overlap syndrome associated with a CYLD gene variant.Case:We describe the case of a 59-year-old male patient who presented with slowing of movements and hypophonic speech. Neurological examination revealed hypomimia, dysarthric and hypophonic speech, restricted upward gaze, slow saccadic eye movements, rigidity and bradykinesia in all extremities, axial rigidity, brisk deep tendon reflexes, bilateral positive Hoffman’s sign, and bilateral extensor plantar responses. Brain MRI showed the “hummingbird sign” accompanied by bilateral cortico-spinal tract hyperintensity. MEP studies showed impaired excitability and conduction in the corticomotor system. Molecular genetic analysis identified a heterozygous G107A (c.320G>A; p.Gly107Asp) missense variant in the CYLD gene.Conclusion:Based on these findings, a diagnosis of PSP-Primary Lateral Sclerosis overlap syndrome was made. The contribution of the identified CYLD variant to this complex phenotype and its role in the neurodegenerative disease spectrum warrant further investigation.

Distribution of ABCB1 Genetic Variants and their Association with Moxifloxacin Pharmacokinetics in Hospitalized Patients with Acute Exacerbation of COPD

Wed, 14 Oct 2026 00:00:00 GMT

Interindividual variability in moxifloxacin pharmacokinetics may contribute to differences in therapeutic response and has been partially attributed to genetic factors affecting drug transport. The present study investigated the distribution of three common ABCB1 polymorphisms, c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642), and explored their association with moxifloxacin pharmacokinetics in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Thirty adult patients receiving intravenous moxifloxacin 400 mg once daily were included. Plasma concentrations were quantified using a validated HPLC–UV method, and individual pharmacokinetic parameters were obtained from a previously developed population pharmacokinetic model. Genotyping was performed using TaqMan SNP Genotyping Assays. Genotype, allele and haplotype frequencies were compared with previously published data from a healthy Macedonian population. The observed genotype and allele frequencies were comparable to those reported in healthy individuals. Minor allele frequencies were 43.3% for c.1236C>T, 41.6% for c.2677G>T/A, and 45.0% for c.3435C>T. Two predominant haplotypes were identified: CGC (56.7%) and TTT (43.3%). Differences in moxifloxacin exposure were observed between genotype groups. For c.1236C>T, heterozygous carriers demonstrated the highest mean exposure, with a mean AUC of 56.24 mg·h/L and the lowest CL (9.55 L/h), whereas wild-type carriers had a lower mean AUC (37.57 mg·h/L). Similar trends were observed for c.2677G>T/A. Although limited by the small sample size, the findings suggest that ABCB1 genetic variability may contribute to interindividual differences in moxifloxacin pharmacokinetics and warrant further investigation in larger patient cohorts.

Multiple Basal Cell Carcinomas in an Adolescent with an MLPA-Detected PTCH1-Region Deletion and a Gorlin-Goltz Phenotype

Wed, 14 Oct 2026 00:00:00 GMT

Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome or basal cell naevus syndrome, is a rare hereditary cancer-predisposition disorder most often caused by disruption of the Hedgehog signaling pathway, particularly alterations of PTCH1. Classical disease is characterized by multiple or early-onset basal cell carcinomas, odontogenic keratocysts, palmoplantar pits, skeletal anomalies and intracranial calcifications. Deletions involving chromosome region 9q22.3 may create an overlapping but broader phenotype because the deleted interval may include PTCH1 together with neighboring genes.Hereby we report a 15-year-old female patient with developmental disability, including a specific speech articulation disorder, who presented with multiple facial erosions, scars, milia, papulo-nodular lesions and palmar pitting. Dermoscopy demonstrated arborizing vessels, blue-gray ovoid nests, brown dots, ulceration, white scales and shiny white perpendicular lines. Surgical excision of selected lesions was performed, and histopathology confirmed basal cell carcinoma in three specimens, reported as carcinoma basocellulare. Additional findings included a nasal-root dermoid cyst excised in early childhood, strabismus, conductive hearing loss, kyphoscoliosis and a kinked aorta. Multiplex ligation-dependent probe amplification (MLPA) using the SALSA MLPA Probemix P245-A2 Microdeletion Syndromes-1 (MRC-Holland, Amsterdam, The Netherlands) demonstrated a deletion involving the PTCH1 region at chromosome 9q22.3.This case is highly suggestive of a PTCH1-region deletion presenting with a Gorlin-Goltz phenotype, with additional extracutaneous findings that may reflect involvement of the wider 9q22.3 region; because MLPA cannot delineate deletion boundaries or confirm loss of neighboring genes, this broader interpretation remains presumptive pending array-based confirmation. The occurrence of multiple basal cell carcinomas in adolescence should prompt evaluation for inherited tumor-predisposition syndromes. When extracutaneous developmental or congenital abnormalities are present, genetic testing capable of detecting and mapping copy-number variants should be considered.

Development and Validation of PCR-Based Ancient DNA Analysis for Italian and Western Balkan Archaeological Collections

Wed, 14 Oct 2026 00:00:00 GMT

Introduction:The Italian Peninsula and Western Balkans preserve rich archaeological records that extend from pre-Roman times through the Greek colonial, Roman, and Byzantine periods. Genetic investigation of these collections often requires access to specialized high-throughput technologies which are not commonly available or cost-effective method to handle the problem of broken skeletal remains.Methods:We developed and validated an ancient DNA protocol for Italian and Albanian archeological skeletal samples spanning approximately 2500 years. The protocol included artificial fragmentation of modern DNA to simulate ancient molecular profiles and validation using archaeological remains from Sicily, Rome and Apollonia. The workflow integrated EDTA demineralization, silica-based purification, PCR targeting short amplicons (<150 bp) to enable sex determination, species authentication, uniparental haplogroup analysis, and pigmentation trait prediction. Strict anti-contamination and authentication criteria were enforced.Results:Amplifiable DNA was recovered from all tested skeletal samples. Mitochondrial DNA haplogroups were assigned in 82%, while Y-chromosome markers were found in 76% of males, while sex was determined in 85% of the samples. Pigmentation SNPs yielded complete profiles in 78%. Amplicons <110 bp showed >90% amplification success. All results were reproducible and met authentication criteria, including phylogenetic plausibility and inverse fragment length-yield correlation.Conclusion:This protocol enables ancient DNA analysis from degraded skeletal remains of Mediterranean archaeological contexts. The simulated ancient DNA presents a key innovation, allowing refinement of procedures before application to irreplaceable material and provides a practical approach for laboratories with limited access to High-Throughput sequencing. The research is a practical framework for studying mobility, ancestry and demography among ancient populations from the Mediterranean and Western Balkan regions.

Identification of Peripheral Blood mIR-128-3p Molecular Signature in Children with Autism Spectrum Disorder

Wed, 14 Oct 2026 00:00:00 GMT

MicroRNAs (miRNAs) are key post-transcriptional regulators of gene expression. Given the dynamic nature of the peripheral blood transcriptome, profiling circulating miRNAs in autism spectrum disorder (ASD) represents a promising strategy for identifying novel disease-associated biomarkers. Large-scale miRNA expression profiling was performed using the μParaflo™ miRNA microarray assay on pooled RNA samples from 23 individuals with ASD and 21 healthy controls. Differential expression analysis (p < 0.05) identified several dysregulated miRNAs in peripheral blood, including miR-128-3p. Microarray findings for miR-128-3p were validated by quantitative reverse transcription PCR (qRT-PCR), which confirmed its significant downregulation in the ASD group. Target gene analysis using miRWalk indicated that miR-128-3p exerts multilevel regulatory effects across diverse biological processes. Notably, predicted and validated targets included genes involved in neuronal development (e.g., PTEN) and epigenetic regulation (e.g., DNMT1, RNASEN, DICER, and EIF2C2). Receiver operating characteristic (ROC) curve analysis demonstrated significant diagnostic potential of miR-128-3p for ASD. Collectively, these findings support an integrative model of ASD as a heterogeneous neurodevelopmental disorder in which specific miRNAs, such as miR-128-3p, contribute to disease pathogenesis through modulation of gene expression networks.

Townes–Brocks Syndrome With Consistent Renal Hypodysplasia and Variable Extrarenal Features Across Three Generations of Serbian Family

Thu, 14 May 2026 00:00:00 GMT

BackgroundTownes–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.ResultsWe 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.ConclusionThis 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.

Shared Inflammatory Gene Programs between Immune Thrombocytopenia and CKD-Related Autoimmune Nephropathies: An Exploratory Transcriptomic and Bioinformatic Study

Thu, 14 May 2026 00:00:00 GMT

ObjectiveTo 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).MethodsCD19+ 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.ResultsIntersecting 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.ConclusionsNewly 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.

Exploratory Analysis of Sex-Related Immune Gene Expression in Patients With Severe Periodontitis

Thu, 14 May 2026 00:00:00 GMT

BackgroundBiological 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.MethodsTen 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).ResultsAmong 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.ConclusionThese 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.

Beyond Living Donor Kidney Transplantation in COL4 Nephropathy - A Real-World Clinical Dilemma in Light of Current Guidelines

Thu, 14 May 2026 00:00:00 GMT

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.

Secretory Breast Carcinoma in A Six-Year-Old Girl: Case Report With Genetic Insights and Therapeutic Implications

Thu, 14 May 2026 00:00:00 GMT

BackgroundSecretory 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 PresentationWe 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 FindingsGermline 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 ImplicationsThe 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.OutcomeSix years after surgery, the patient remains disease-free without evidence of recurrence or metastasis.ConclusionThis 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.

Impact of Cholecystectomy on Gastric Mucosal c-MYC and h-TERT Expression; A Potential Link to Gastric Cancer Development

Thu, 14 May 2026 00:00:00 GMT

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.