Markusovszky Egyetemi Oktatókórház

PAX6 haploinsufficiency-related congenital aniridia is frequently associated with ocular surface disease, including meibomian gland dysfunction (MGD), dry eye, limbal stem cell deficiency (LSCD), aniridia-associated keratopathy (AAK), and inflammation. This study measured ocular surface temperature (OST) at the corneal center and four paracentral points (2 mm from center) in patients with congenital aniridia and examined factors influencing OST. Forty-five eyes from 26 aniridia patients (55.6% female; 26.29 ± 17.78 years) with PAX6 pathogenic variants and 47 eyes from 25 controls (68.1% female; 24.81 ± 4.73 years; p = 0.1639) were included. Body temperature, OSDI, and OST (TG-1000) were recorded; clinical assessment evaluated MGD, LSCD, AAK, iris malformation, epithelial defects, Salzmann nodules, glaucoma and previous ocular surgery. Body temperature and OSDI did not differ in aniridia and controls (p ≥ 0.606). LSCD was mainly Grade 2 (46.7%) or Grade 4 (40.0%), and AAK Grade 1 (33.3%) or Grade 2 (31.1%). MGD affected 51.1%, Salzmann nodules 22.2%, epithelial defects 2.2%, glaucoma 60.0%, and previous ocular surgery 35.5%. Superior OST was higher in aniridia (34.98 ± 0.55 °C vs. 34.75 ± 0.47 °C; p = 0.012). Exploratory univariate analyses identified that higher AAK grade correlated with lower inferior OST (p = 0.030), iris malformation with reduced central/paracentral OST (p ≤ 0.029), and Salzmann nodules with lower OST overall (p ≤ 0.011). However, in a multivariate model, age, Salzmann nodular degeneration, and prior ocular surgery emerged as key determinants of OST. OST may serve as a noninvasive biomarker in congenital aniridia.

In recent years, targeted therapies have become the standard of care for refractory/relapsed mantle cell lymphoma (MCL). Although the mutational profile of MCL has been extensively studied, there is a lack of understanding of resistance mechanisms and genetic factors that impact the response to novel treatments. Since patients relapsing on targeted treatment experience poor clinical outcomes, understanding the genetic foundation of resistance mechanisms in MCL is essential. In this study, we aimed to scrutinize the copy number profile and clonal dynamics of double-resistant MCL patients treated sequentially with Bruton's tyrosine kinase inhibitor (BTKi) and venetoclax using low-coverage whole genome sequencing (lcWGS). Samples obtained after systemic therapy showed more copy number alterations (CNAs) (p = 0.039; Wilcoxon) compared to samples collected before treatment initiation. Patients showing early progression on BTKi demonstrated CNAs affecting cytobands encompassing the coding regions of NOTCH1, TRAF2, BIRC2, BIRC3, and ATM. A deletion in chromosome 9p21.3 was identified in two out of three venetoclax-resistant patients. For patient MCL2, progressing on ibrutinib but showing venetoclax resistance, a 9p21.3 deletion was found throughout the disease course, with acquired SMARCA4-del(19)(p13.3-q13.11) and DLC1-del(8)(p23.2-q11.1) observed at relapse, highlighting their role in disease progression and therapy resistance. Using lcWGS, an innovative genome-wide approach, this study revealed novel putative primary and acquired resistance mechanisms in BTKi and venetoclax double-resistant MCL patients. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Genetic services have not been evenly distributed in Hungary. Diagnostic services for rare diseases have particularly been scarce in the West end of the country. We aimed to fill this diagnostic gap. We have created a new mod- el involving the molecular medicine (MM) service as a tertiary patient referral center at the Markusovszky University Teaching Hospital (MUTH) in contract with the Ge- nomics and Bioinformatics Core Facility of the Szentágothai Research Center, University of Pécs, and the iBioScience company, which provide whole exome sequencing and Sanger sequencing. We present our results of molecular genetic and genomic diagnostics for rare neurological diseases, and highlight a few cases where the identification of the caus- ative pathogenic or likely pathogenic variant resulted in direct benefit to the patient. Our multidisciplinary collab- oration operating in less than two years has filled a gap in genetic services in the West-Hungary region, and yielded shortcuts to diagnostics, led to targeted therapy and supported family planning in several cases with rare neurological diseases.

Abstract Transgender and gender-diverse (TGD) individuals are at a greater risk for various poor mental and behavioral health outcomes than cisgender individuals, including higher rates of suicide, psychiatric diagnoses, and behavioral health problems. For example, research has documented a seven-fold increased risk for lifetime suicide attempts among young TGD people, compared with the general population. Less is known about the age of onset of such mental and behavioral health disparities and how these disparities may vary across other intersectional socio-demographic variables. It has been well-documented that trans and gender-diverse individuals often encounter discrimination and transphobia across various social, educational, professional, administrative, and healthcare settings. This discrimination, as highlighted in the literature, frequently poses obstacles to accessing both general and trans-specific healthcare services due to experiences of discrimination (e.g., misgendering, refusal of care, lack of adequate services). The right and ability to self-determine and the accessibility to gender-affirming care without discrimination are key to closing the gap in TGD individuals’ mental and behavioral health outcomes, and for them to live authentically and thrive. Tailored and affirming mental and behavioral health interventions to reduce these health inequities are pivotal for TGD individuals to achieve the highest attainable standard of physical and mental health: a key fundamental human right. Considerable gaps in the literature remain concerning the onset and determinants of gender identity-based health disparities and healthcare approaches that are respectful, inclusive, non-pathologizing, and grounded in human rights principles for TGD individuals. This workshop intends to address these knowledge gaps by delving into the mental and behavioral health needs of TGD individuals. The workshop seeks to further foster dialogue on strategies to overcome resistance to implementing approaches that uphold the human rights and well-being of these communities. Dr. Richard Bränström (Karolinska Institutet) will present a study that explores the age at which gender identity-based disparities in psychiatric diagnoses and treatment can be first identified. Dr. Gonzales (Vanderbilt University) will examine disparities in mental health and social determinants of health among TGD individuals with private insurance. Dr. Moleiro (Lisbon University Institute) will review TGD persons’ ways of identifying with the choices and trajectories in social, legal, and affirmative healthcare processes in Portugal. Dr. Lelutiu-Weinberger (Columbia University School of Nursing) will present findings from a study that assessed tobacco use and cessation attitudes, facilitators, and barriers to quitting, and intervention components and delivery modality acceptability among TGD individuals, as well as sexual minority individuals, in Romania to inform a tailored and affirming smoking cessation intervention. Key messages • Transgender and gender-diverse are at increased risk for a variety of poor mental and behavioral health compared with the general public. • There is a critical need to foster healthcare services for transgender and gender-diverse individuals that are tailored and affirming.

OMICS methods brought significant advancements to the understanding of tumor cell biology, which transformed the treatment and prognosis of several cancers. Clinical practice and outcomes, however, changed significantly less in the case of glioblastoma (GBM). In this study, we aimed to assess the utility of whole exome (WES) sequencing in the clinical setting. Ten pairs of formalin-fixed, paraffin-embedded (FFPE) GBM specimens were obtained at onset (GBM-P) and at recurrence (GBM-R). Histopathological and molecular features of all samples supported the diagnosis of GBM based on WHO CNS5. WES data were filtered, applying a strict and custom-made pipeline, and occurrence of oncogenic and likely oncogenic variants in GBM-P, GBM-R or both were identified by using the VarSeq program version 2.5.0 (Golden Helix, Inc.). Characteristics and recurrence of the variants were analyzed in our own cohort and were also compared to those available in the COSMIC database. The lists of oncogenic and likely oncogenic variants corresponded to those identified in other studies. The average number of these variants were 4 and 5 out of all detected 24 and 34 variants in GBM-P and GBM-R samples, respectively. On average, one shared oncogenic/likely oncogenic variant was found in the pairs. We assessed the identified variants' therapeutic significance, also taking into consideration the guidelines by the Association for Molecular Pathology (AMP). Our data support that a thorough WES analysis is suitable for identifying oncogenic and likely oncogenic variants in an individual clinical sample or a small cohort of FFPE glioma specimens, which concur with those of comprehensive research studies. Such analyses also allow us to monitor molecular dynamics of sequential GBM. In addition, careful evaluation of data according to the AMP guideline reveal that though therapeutic applicability of the variants is generally limited in the clinic, such information may be valuable in selected cases, and can support innovative preclinical and clinical trials.

Psoriasis is a common, life-long skin disease with a significant negative health and societal impact. Data on rates of disease control and treatment strategies are lacking in Central and Eastern European countries. We aimed to describe the real-world disease severity, control, and treatment strategies for psoriasis in patients from Central and Eastern European countries. CRYSTAL (EUPAS36459) was a cross-sectional, retrospective study in adults (18-75 years) from Bulgaria, Estonia, Hungary, Latvia, Lithuania, Romania, and Russia. We enrolled patients with moderate-to-severe psoriasis receiving continuous systemic treatment for ≥24 weeks. We used the Psoriasis Area and Severity Index (PASI) to describe disease severity and the Dermatology Life Quality Index (DLQI) to assess quality of life (QoL) and collected other outcomes [psoriasis work productivity and activity impairment (WPAI-PSO), patient satisfaction] at enrollment. Analyses were descriptive. A total of 690 patients were included in the analyses. Median disease duration was 11.8 years. Current treatment was monotherapy for most patients (95.8%) with either biological (BIO group; 88.4%) or conventional (NON-BIO group; 7.4%) agents. Mean (± standard deviation) absolute PASI scores were 3.5 ± 5.7, 3.1 ± 5.3, and 6.6 ± 7.4 in the overall population, the BIO group, and the NON-BIO group, respectively. Among patients treated with monotherapy, absolute PASI scores ≤1, ≤3, and ≤5 were observed for 44.1%, 72.0%, and 82.6% of BIO patients and 21.6%, 33.3%, and 49.0% of NON-BIO patients. Mean DLQI total score was 3.3 ± 5.1; higher scores were noted for higher absolute PASI. The most impacted WPAI-PSO domain was presenteeism; for all domains, impact increased with increased absolute PASI. A total of 91.8% of BIO patients and 74.5% of NON-BIO patients were satisfied with the current treatment. We observed a better disease control in BIO than NON-BIO patients. However, around half of BIO patients did not reach clear skin status and reported an impact on QoL. An improvement in treatment strategies is still needed in Central and Eastern European countries to optimize outcomes of moderate-to-severe psoriasis.

Introduction: One of the major technological innovations of the last decade has been the proliferation of high-throughput molecular genetic testing methods, such as chromosomal microarray analysis (CMA) and whole-exome sequencing (WES) in prenatal diagnostics. Objective: Over the past 5 years, our working group has performed more than 252 prenatal examinations, indicated by ultrasound abnormalities of varying severity. Depending on the results of classical cytogenetic studies, we performed high-resolution CMA and WES analyses, with the aim to map the proportion of excess genetic information in the Hungarian population, as described in the literature. Method: CMA studies were performed using the “GeneChip System 3000 Instrument” platform with SNP-based comparative hybridization. We also performed next-generation sequencing of the whole human exome using IonTorrent and Illumina platforms. Results: A total of 252 fetal CMA examinations were performed and 42% showed some loss or gain, of which 22% showed pathogenic abnormalities. We performed WES in 42 CMA-negative cases, of which 9 (21.4%) were identified as pathogenic abnormalities supporting the inheritance process, with presumed association with fetal phenotype, based on the ClinVar database or ACMG classification. Discussion: Given the indirect nature of fetal phenotype assessment, prenatal CMA and WES analysis should be limited primarily to genes and chromosomal regions associated with ultrasound-identifiable symptoms. Parental examination is of paramount importance in both CMA and WES analyses, especially in cases where the resulting disorder cannot be clearly associated with ultrasound abnormalities. Conclusion: It is important to define the parameters by which copy number variations are detected in fetal samples. Recommendations for reporting variants confirmed by WES testing should also be given (taking international recommendations into account). These will provide more useful information for prenatal clinical genetic counselling. Orv Hetil. 2024; 165(14): 523–530.