Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (765)

Search Parameters:
Keywords = rare genotypes

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
18 pages, 978 KiB  
Review
NUDT15 Pharmacogenetics in Acute Lymphoblastic Leukemia: Synthesizing Progress for Personalized Thiopurine Therapy
by Isfahan Shah Lubis, Kusnandar Anggadiredja, Aluicia Anita Artarini, Nur Melani Sari, Nur Suryawan and Zulfan Zazuli
Med. Sci. 2025, 13(3), 112; https://doi.org/10.3390/medsci13030112 - 5 Aug 2025
Abstract
The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies [...] Read more.
The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article
Show Figures

Figure 1

17 pages, 7038 KiB  
Article
Polyploidy Induction of Wild Diploid Blueberry V. fuscatum
by Emily Walter, Paul M. Lyrene and Ye Chu
Horticulturae 2025, 11(8), 921; https://doi.org/10.3390/horticulturae11080921 (registering DOI) - 5 Aug 2025
Abstract
Diploid Vaccinium fuscatum is a wild blueberry species with a low chilling requirement, an evergreen growth habit, and soil adaptability to southeast US growing regions. Regardless of its potential to improve the abiotic and biotic resilience of cultivated blueberries, this species has rarely [...] Read more.
Diploid Vaccinium fuscatum is a wild blueberry species with a low chilling requirement, an evergreen growth habit, and soil adaptability to southeast US growing regions. Regardless of its potential to improve the abiotic and biotic resilience of cultivated blueberries, this species has rarely been used for blueberry breeding. One hurdle is the ploidy barrier between diploid V. fuscatum and tetraploid cultivated highbush blueberries. To overcome the ploidy barrier, vegetative shoots micro-propagated from one genotype of V. fuscatum, selected because it grew vigorously in vitro and two southern highbush cultivars, ‘Emerald’ and ‘Rebel,’ were treated with colchicine. While shoot regeneration was severely repressed in ‘Emerald’ and ‘Rebel,’ shoot production from the V. fuscatum clone was not compromised at either 500 µM or 5000 µM colchicine concentrations. Due to the high number of shoots produced in vitro via the V. fuscatum clone shoots of this clone that had an enlarged stem diameter in vitro were subjected to flow cytometer analysis to screen for induced polyploidy. Sixteen synthetic tetraploid V. fuscatum, one synthetic octoploid ‘Emerald,’ and three synthetic octoploid ‘Rebel’ were identified. Growth rates of the polyploid-induced mutants were reduced compared to their respective wildtype controls. The leaf width and length of synthetic tetraploid V. fuscatum and synthetic octoploid ‘Emerald’ was increased compared to the wildtypes, whereas the leaf width and length of synthetic octoploid ‘Rebel’ were reduced compared to the wildtype controls. Significant increases in stem thickness and stomata guard cell length were found in the polyploidy-induced mutant lines compared to the wildtypes. In the meantime, stomata density was reduced in the mutant lines. These morphological changes may improve drought tolerance and photosynthesis in these mutant lines. Synthetic tetraploid V. fuscatum can be used for interspecific hybridization with highbush blueberries to expand the genetic base of cultivated blueberries. Full article
(This article belongs to the Section Propagation and Seeds)
Show Figures

Figure 1

13 pages, 462 KiB  
Article
Genetic Landscape of Congenital Cataracts in a Swiss Cohort: Addressing Diagnostic Oversights in Nance–Horan Syndrome
by Flora Delas, Jiradet Gloggnitzer, Alessandro Maspoli, Lisa Kurmann, Beatrice E. Frueh, Ivanka Dacheva, Darius Hildebrand, Wolfgang Berger and Christina Gerth-Kahlert
Biomedicines 2025, 13(8), 1883; https://doi.org/10.3390/biomedicines13081883 - 2 Aug 2025
Viewed by 261
Abstract
Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in [...] Read more.
Congenital cataracts (CCs) are a leading cause of preventable childhood blindness, with genetic factors playing a crucial role in their etiology. Nance–Horan syndrome (NHS) is a rare X-linked dominant disorder associated with CCs but is often underdiagnosed due to variable expressivity, particularly in female carriers. Objective: This study aimed to explore the genetic landscape of CCs in a Swiss cohort, focusing on two novel NHS and one novel GJA8 variants and their phenotypic presentation. Methods: Whole-exome sequencing (WES) was conducted on 20 unrelated Swiss families diagnosed with CCs. Variants were analyzed for pathogenicity using genetic databases, and segregation analysis was performed. Clinical data, including cataract phenotype and associated systemic anomalies, were assessed to establish genotype–phenotype correlations. Results: Potentially pathogenic DNA sequence variants were identified in 10 families, including three novel variants, one in GJA8 (c.584T>C) and two NHS variants (c.250_252insA and c.484del). Additional previously reported variants were detected in CRYBA1, CRYGC, CRYAA, MIP, EPHA2, and MAF, reflecting genetic heterogeneity in the cohort. Notably, NHS variants displayed significant phenotypic variability, suggesting dose-dependent effects and X-chromosome inactivation in female carriers. Conclusions: NHS remains underdiagnosed due to its variable expressivity and the late manifestation of systemic features, often leading to misclassification as isolated CC. This study highlights the importance of genetic testing in unexplained CC cases to improve early detection of syndromic forms. The identification of novel NHS and GJA8 variants provides new insights into the genetic complexity of CCs, emphasizing the need for further research on genotype–phenotype correlations. Full article
(This article belongs to the Special Issue Ophthalmic Genetics: Unraveling the Genomics of Eye Disorders)
Show Figures

Figure 1

13 pages, 1397 KiB  
Article
RSPH4A-PCDx: An Index to Predict Lung Function Decline in Primary Ciliary Dyskinesia
by Gabriel Román-Ríos, Gabriel Rosario-Ortiz, Marcos J. Ramos-Benitez, Ricardo A. Mosquera and Wilfredo De Jesús-Rojas
Adv. Respir. Med. 2025, 93(4), 27; https://doi.org/10.3390/arm93040027 - 2 Aug 2025
Viewed by 164
Abstract
Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with RSPH4A-associated PCD and to [...] Read more.
Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous disorder that impairs mucociliary clearance and leads to progressive lung disease. This study aimed to characterize lung function decline in a genetically homogeneous cohort of Puerto Rican patients with RSPH4A-associated PCD and to develop a clinical tool to predict lung function decline and support transplant referral decisions. We conducted a retrospective chart review of patients (n = 25) with a confirmed RSPH4A [c.921+3_6delAAGT] genetic variant, collecting longitudinal spirometry data and applying linear regressions to calculate each patient’s individual FEV1 decline. The median FEV1 at diagnosis was 55%, with a median annual decline of −0.75% predicted. Adults exhibited significantly lower lung function compared to pediatric patients, while no difference was seen between males and females. Based on this observed decline, we developed the Predicted Capacity Decline Index (PCDx), an index that estimates the age and time until a patient reaches the 30% FEV1 threshold, the point at which lung transplant referral is typically considered. Our findings underscore the need for early intervention and suggest that genotype-specific tools like the PCDx may enhance clinical decision-making in managing progressive lung disease in PCD. Full article
Show Figures

Figure 1

12 pages, 1990 KiB  
Article
Vaginal Intraepithelial Neoplasia (VaIN)—A Retrospective Cohort Analysis of Epidemiology, Risk Factors, and Management in an Academic Clinical Center
by Barbara Suchońska, Franciszek Ługowski, Magdalena Papież and Artur Ludwin
J. Clin. Med. 2025, 14(15), 5386; https://doi.org/10.3390/jcm14155386 - 30 Jul 2025
Viewed by 256
Abstract
Background: Vaginal intraepithelial neoplasia (VaIN) is a rare but potentially precancerous condition strongly associated with human papillomavirus (HPV) infection. Despite increased detection rates due to HPV screening and colposcopy, diagnosis and management remain challenging. This study aimed to evaluate the epidemiological characteristics, [...] Read more.
Background: Vaginal intraepithelial neoplasia (VaIN) is a rare but potentially precancerous condition strongly associated with human papillomavirus (HPV) infection. Despite increased detection rates due to HPV screening and colposcopy, diagnosis and management remain challenging. This study aimed to evaluate the epidemiological characteristics, risk factors, and outcomes of VaIN in patients referred to a tertiary academic center. Methods: We conducted a retrospective analysis of 48 patients who underwent colposcopy-directed vaginal biopsies between January 2019 and June 2024 at the Medical University of Warsaw. Data collected included patient demographics, HPV status, cytology, histopathology, and treatment outcomes. Patients were grouped based on the presence and grade of VaIN (VaIN 1 vs. VaIN 2/3). Statistical analyses were performed using SPSS software. Results: VaIN was diagnosed in 24 patients (50%), VaIN was confirmed in half of the cohort, VaIN 2 in 30%, and VaIN 3 in 18% of cases. HPV infection and prior cervical pathology were significantly associated with VaIN diagnosis (P = 0.03 and P = 0.05, respectively), and high-risk HPV infection correlated with higher-grade lesions (P = 0.04). Among VaIN 2+ cases, most patients required laser ablation or surgical excision, while VaIN 1 often regressed spontaneously. Regression occurred in 11 cases, and high-risk HPV infection was inversely associated with spontaneous regression (P = 0.04). Conclusions: This study confirms the central role of HPV, particularly high-risk subtypes, in VaIN pathogenesis. Conservative management may be appropriate for VaIN 1, while VaIN 2+ requires active intervention. HPV genotyping should be integrated into diagnostic workups, and long-term follow-up is essential due to the risks of persistence and recurrence. Full article
Show Figures

Figure 1

13 pages, 1323 KiB  
Article
Genotypic and Phenotypic Characterization of Axonal Charcot–Marie–Tooth Disease in Childhood: Identification of One Novel and Four Known Mutations
by Rojan İpek, Büşra Eser Çavdartepe, Sevcan Tuğ Bozdoğan, Erman Altunışık, Akçahan Akalın, Mahmut Yaman, Alper Akın and Sefer Kumandaş
Genes 2025, 16(8), 917; https://doi.org/10.3390/genes16080917 - 30 Jul 2025
Viewed by 272
Abstract
Background: Charcot–Marie–Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. Methods: This retrospective study included five pediatric patients [...] Read more.
Background: Charcot–Marie–Tooth disease (CMT) is a genetically and phenotypically heterogeneous hereditary neuropathy. Axonal CMT type 2 (CMT2) subtypes often exhibit overlapping clinical features, which makes molecular genetic analysis essential for accurate diagnosis and subtype differentiation. Methods: This retrospective study included five pediatric patients who presented with gait disturbance, muscle weakness, and foot deformities and were subsequently diagnosed with axonal forms of CMT. Clinical data, electrophysiological studies, neuroimaging, and genetic analyses were evaluated. Whole exome sequencing (WES) was performed in three sporadic cases, while targeted CMT gene panel testing was used for two siblings. Variants were interpreted using ACMG guidelines, supported by public databases (ClinVar, HGMD, and VarSome), and confirmed by Sanger sequencing when available. Results: All had absent deep tendon reflexes and distal muscle weakness; three had intellectual disability. One patient was found to carry a novel homozygous frameshift variant (c.2568_2569del) in the IGHMBP2 gene, consistent with CMT2S. Other variants were identified in the NEFH (CMT2CC), DYNC1H1 (CMT2O), and MPV17 (CMT2EE) genes. Notably, a previously unreported co-occurrence of MPV17 mutation and congenital heart disease was observed in one case. Conclusions: This study expands the clinical and genetic spectrum of pediatric axonal CMT and highlights the role of early physical examination and molecular diagnostics in detecting rare variants. Identification of a novel IGHMBP2 variant and unique phenotypic associations provides new insights for future genotype–phenotype correlation studies. Full article
(This article belongs to the Special Issue Genetics of Neuromuscular and Metabolic Diseases)
Show Figures

Figure 1

21 pages, 1997 KiB  
Article
Genetic and Metabolic Factors of Familial Dysbetalipoproteinemia Phenotype: Insights from a Cross-Sectional Study
by Anastasia V. Blokhina, Alexandra I. Ershova, Anna V. Kiseleva, Evgeniia A. Sotnikova, Marija Zaicenoka, Anastasia A. Zharikova, Yuri V. Vyatkin, Vasily E. Ramensky, Elizaveta A. Novokhatskaya, Anna L. Borisova, Svetlana A. Shalnova, Alexey N. Meshkov and Oxana M. Drapkina
Int. J. Mol. Sci. 2025, 26(15), 7376; https://doi.org/10.3390/ijms26157376 - 30 Jul 2025
Viewed by 137
Abstract
Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and [...] Read more.
Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article
(This article belongs to the Special Issue Genes and Human Diseases: 3rd Edition)
Show Figures

Figure 1

10 pages, 1920 KiB  
Case Report
Junctional Epidermolysis Bullosa Caused by a Hemiallelic Nonsense Mutation in LAMA3 Revealed by 18q11.2 Microdeletion
by Matteo Iacoviello, Marilidia Piglionica, Ornella Tabaku, Antonella Garganese, Aurora De Marco, Fabio Cardinale, Domenico Bonamonte and Nicoletta Resta
Int. J. Mol. Sci. 2025, 26(15), 7343; https://doi.org/10.3390/ijms26157343 - 29 Jul 2025
Viewed by 293
Abstract
Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the [...] Read more.
Inherited epidermolysis bullosa (EB) is a heterogeneous clinical entity that includes over 30 phenotypically and/or genotypically distinct inherited disorders, characterized by mechanical skin fragility and bullae formation. Junctional EB (JEB) is an autosomal recessive disease characterized by an intermediated cleavage level within the skin layers, commonly at the “lamina lucida”. Laryngo-onycho-cutaneous syndrome (LOC) is an extremely rare variant of JEB, characterized by granulation tissue formation in specific body sites (skin, larynx, and nails). Although most cases of JEB are caused by pathogenic variants occurring in the genes encoding for classical components of the lamina lucida, such as laminin 332 (LAMA3, LAMB3, LAMC2), integrin α6β4 (ITGA6, ITGB4), and collagen XVII (COL17A1), other variants have also been described. We report the case of a 4-month-old male infant who presented with recurrent bullous and erosive lesions from the first month of life. At the first dermatological evaluation, the patient was agitated and exhibited hoarse breathing, a clinical sign suggestive of laryngeal involvement. Multiple polygonal skin erosions were observed on the cheeks, along with similar isolated, roundish lesions on the scalp and legs. Notably, nail dystrophy and near-complete anonychia were evident on the left first and fifth toes. Due to the coexistence of skin erosions and nail dystrophy in such a young infant, a congenital bullous disorder was suspected, prompting molecular analysis of all potentially involved genes. In the patient’s DNA, clinical exome sequencing (CES) identified a pathogenic variant, apparently in homozygosity, in the exon 1 of the LAMA3 gene (18q11.2; NM_000227.6): c.47G > A;p.Trp16*. The presence of this variant was confirmed, in heterozygosity, in the genomic DNA of the patient’s mother, while it was absent in the father’s DNA. Subsequently, trio-based SNP array analysis was performed, revealing a paternally derived pathogenic microdeletion encompassing the LAMA3 locus (18q11.2). To our knowledge, this is the first reported case of JEB with a LOC-like phenotype caused by a maternally inherited monoallelic nonsense mutation in LAMA3, unmasked by an almost complete deletion of the paternal allele. The combined use of exome sequencing and SNP array is proving essential for elucidating autosomal recessive diseases with a discordant segregation. This is pivotal for providing accurate genetic counseling to parents regarding future pregnancies. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
Show Figures

Figure 1

18 pages, 670 KiB  
Article
Genetic Heterogeneity Correlated with Phenotypic Variability in 48 Patients with Cystic Fibrosis
by Mădălina Andreea Donos, Lăcrămioara Ionela Butnariu, Dana Teodora Anton Păduraru, Alina Mariela Murgu, Cristina Rusu, Monica Cristina Pânzaru, Roxana Popescu, Elena Țarcă, Elena Cojocaru, Gabriela Ghiga and Laura Mihaela Trandafir
J. Clin. Med. 2025, 14(15), 5362; https://doi.org/10.3390/jcm14155362 - 29 Jul 2025
Viewed by 220
Abstract
Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in [...] Read more.
Background/Objectives: Cystic fibrosis (CF) is a rare autosomal recessive genetic disease that has a progressive and multisystemic course. The spectrum and frequency of mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) vary both in European countries and in other geographical regions. The aim of our retrospective study was to present the genetic variants identified in a group of 48 CF patients from the Moldova region (Romania), as well as to establish genotype–phenotype correlations. Methods: Genetic testing was initially performed for 38 CFTR mutations, and in heterozygous patients or those in whom no mutation was detected, CFTR gene sequencing (NGS) was performed. Results: The compound heterozygous genotype was identified in 26 (54.16%) of the patients (with one of the alleles being F508del), while 22 (45.83%) patients had the homozygous F508del genotype. The F508del variant was the most frequent (69.79%), followed by G542X (6.25%, 6/96). Several new variants were also identified that had not been reported in other studies from Romania (R1158X, K598*, R347H, c.2589_2599del, R496H, and CFTRdele2). Phenotypic manifestations in patients with CFTR class I, II, III and VII variants (homozygous and compound heterozygous) were more severe compared to those in patients with CFTR class IV, V and VI mutations, with the data obtained being consistent with those in the literature. Respiratory tract involvement was present in 77.08% of the patients, being more frequent in patients with the compound heterozygous genotype compared to the homozygous F508del genotype. Most patients had exocrine pancreatic insufficiency (EPI) (85.41%). Gastrointestinal manifestations included hepatocytolysis (66.66%) and biliary cirrhosis (0.41%). Meconium ileus was detected in 18.75% of patients, all with a compound heterozygous genotype. Conclusions: We compared the results obtained with data from the literature and correlated the detected CFTR variant (genotype) with the phenotypic manifestations, highlighting certain particularities present in some patients. Genetic testing allows for early diagnosis and adapted management, including personalized treatment for each patient. Identification of novel unclassified CFTR variants still remains a challenge for clinicians. NGS-based screening of heterozygous healthy carriers is important for both genetic counseling and prenatal diagnosis. Full article
(This article belongs to the Special Issue Cystic Fibrosis: Clinical Manifestations and Treatment)
Show Figures

Figure 1

16 pages, 4271 KiB  
Article
Considering Litter Effects in Preclinical Research: Evidence from E17.5 Acid-Sensing Ion Channel 2a Knockout Mice Exposed to Acute Seizures
by Junie P. Warrington, Tyranny Pryor, Maria Jones-Muhammad and Qingmei Shao
Brain Sci. 2025, 15(8), 802; https://doi.org/10.3390/brainsci15080802 - 28 Jul 2025
Viewed by 176
Abstract
Background: The reproducibility of research findings continues to be a challenge in many fields, including neurosciences. It is now required that biological variables such as sex and age be considered in preclinical and clinical research. Rodents are frequently used to model clinical conditions; [...] Read more.
Background: The reproducibility of research findings continues to be a challenge in many fields, including neurosciences. It is now required that biological variables such as sex and age be considered in preclinical and clinical research. Rodents are frequently used to model clinical conditions; however, litter information is rarely presented. Some studies utilize entire litters with each animal treated as an independent sample, while others equally assign animals from each litter to different groups/treatments, and others use averaged data. These methods can yield different results. Methods: This study used different analysis methods to evaluate embryo and placenta weights from E17.5 acid-sensing ion channel 2a (ASIC2a) mice with or without seizure exposure. Results: When each embryo was treated as an individual sample, fetal and placental weight significantly differed following seizures in the ASIC2a heterozygous (+/−) and homozygous (−/−) groups. Differences in fetal weight were driven by females in the ASIC2a+/− group and both sexes in the ASIC2a−/− group. These differences were lost when an average per sex/genotype/litter was used. There was no difference in placental weight when treated individually; however, female ASIC2a−/− placentas weighed less following seizures. This difference was lost with averaged data. ASIC2a−/− fetuses from −/− dams had reduced weights post-seizure exposure. Position on the uterine horn influenced embryo and placental weight. Conclusions: Our results indicate that using full litters analyzed as individual data points should be avoided, as it can lead to Type I errors. Furthermore, studies should account for litter effects and be transparent in their methods and results. Full article
Show Figures

Graphical abstract

18 pages, 1790 KiB  
Case Report
Genotype–Phenotype Correlation Insights in a Rare Case Presenting with Multiple Osteodysplastic Syndromes
by Christos Yapijakis, Iphigenia Gintoni, Myrsini Chamakioti, Eleni Koniari, Eleni Papanikolaou, Eva Kassi, Dimitrios Vlachakis and George P. Chrousos
Genes 2025, 16(8), 871; https://doi.org/10.3390/genes16080871 - 24 Jul 2025
Viewed by 259
Abstract
Background: Osteodysplastic syndromes comprise a very diverse group of clinically and genetically heterogeneous disorders characterized by defects in bone and connective tissue development, as well as in bone density. Here, we report the case of a 48-year-old female with a complex medical history [...] Read more.
Background: Osteodysplastic syndromes comprise a very diverse group of clinically and genetically heterogeneous disorders characterized by defects in bone and connective tissue development, as well as in bone density. Here, we report the case of a 48-year-old female with a complex medical history characterized by bone dysplasia, hyperostosis, and partial tooth agenesis. Methods: Genetic testing was performed using WES analysis and Sanger sequencing. Molecular modeling analysis and dynamics simulation explored the impact of detected pathogenic variants. Results: The genetic analysis detected multiple pathogenic variants in genes CREB3L1, SLCO2A1, SFRP4, LRP5, and LRP6, each of which has been associated with rare osteodysplastic syndromes. The patient was homozygous for the same rare alleles associated with three of the identified autosomal recessive disorders osteogenesis imperfecta type XVI, primary hypertrophic osteoarthropathy, and metaphyseal dysplasia Pyle type. She also had a variant linked to autosomal dominant endosteal hyperostosis and a variant previously associated with increased risk of osteoporosis and bone fractures. Two of the detected variants are predicted to cause abnormal splicing, while molecular modeling and dynamics simulations analysis suggest that the other three variants probably confer altered local secondary structure and flexibility that may have functionally devastating consequences. Conclusions: Our case highlights the rare coexistence of multiple osteodysplastic syndromes in a single patient that may complicate differential diagnosis. Furthermore, this case emphasizes the necessity for early genetic investigation of such complex cases with overlying phenotypic traits, followed by genetic counseling, facilitating orchestration of clinical interventions and allowing prevention and/or prompt management of manifestations. Full article
(This article belongs to the Section Human Genomics and Genetic Diseases)
Show Figures

Figure 1

15 pages, 236 KiB  
Article
Insights into Fanconi Anemia Based on Molecular and Clinical Characteristics: A Multicentre Study of 13 Patients
by Simoni Saranti, Nikoletta Selenti, Christalena Sofocleous, Joanne Traeger-Synodinos, Antonis Kattamis, Vassilios Papadakis, Evgenios Goussetis, Charikleia Kelaidi, Anna Paisiou, Sophia Polychronopoulou and Lydia Kossiva
Children 2025, 12(8), 973; https://doi.org/10.3390/children12080973 - 24 Jul 2025
Viewed by 353
Abstract
Background: Fanconi Anemia (FA) is a rare disorder, characterized by chromosomal instability, congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. FA is caused by pathogenic variants in any of the 23 (FANCA-FANCY) linked genes. Procedure: Retrospective analysis [...] Read more.
Background: Fanconi Anemia (FA) is a rare disorder, characterized by chromosomal instability, congenital abnormalities, progressive bone marrow failure, and predisposition to cancer. FA is caused by pathogenic variants in any of the 23 (FANCA-FANCY) linked genes. Procedure: Retrospective analysis of 13 FA patients with a causative variant was performed. Patients (6 boys and 7 girls) aged from 9 to 26 years old, (mean age of 7.3 years), at diagnosis. Results: Phenotype evaluation demonstrated in 11/13 patients’ congenital anomalies, with pigmentary changes and short stature, present in 90% of cases. Hematological abnormalities were present in 10/11 patients, with thrombocytopenia being the prominent finding. Genetic analysis for the most common complementation group FA-A revealed that 12/13 patients belonged to this group and only one patient was found to be FA-E. Exon deletions, single nucleotide variations, and duplications were identified. Familial patterns, due to consanguinity, were evident in one case. Twelve patients underwent hematopoietic stem cell transplantation (HSCT), with variable pre-HSCT supportive treatments. Post-HSCT data showed that 9 out of 10 patients for whom follow up data was available, survived for a median time of 5.4 years. Complications like acute graft-versus-host disease were noted. Conclusions: Our study highlights the importance of genotype towards tailored monitoring for children and families with FA. Full article
(This article belongs to the Section Pediatric Hematology & Oncology)
6 pages, 454 KiB  
Case Report
ANKRD26 Gene Mutation and Thrombocytopenia—Is the Risk of Malignancy Dependent on the Mutation Variant?
by Eirik B. Tjønnfjord, Kristian Tveten, Signe Spetalen and Geir E. Tjønnfjord
Hematol. Rep. 2025, 17(4), 37; https://doi.org/10.3390/hematolrep17040037 - 24 Jul 2025
Viewed by 255
Abstract
Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid [...] Read more.
Background and Clinical Significance: Inherited thrombocytopenia (IT) is a heterogeneous group of disorders caused by mutations in over 45 genes. Among these, ANKRD26-related thrombocytopenia (ANKRD26-RT) accounts for a notable subset and is associated with variable bleeding tendencies and an increased risk of myeloid malignancies. However, the extent of this oncogenic risk appears to vary between specific gene variants. Understanding the genotype–phenotype relationship is essential for patient counseling and management. This report presents a multigenerational family carrying the rare c.−118C > G variant in the 5′ untranslated region of ANKRD26, contributing to the discussion on variant-specific cancer predisposition. Case Presentation: Two sisters aged 57 and 60 presented with lifelong bleeding diathesis and moderate thrombocytopenia. Their symptoms included easy bruising, menorrhagia, and excessive postoperative bleeding. Genetic testing confirmed heterozygosity for the ANKRD26 c.−118C > G variant. Bone marrow analysis revealed abnormal megakaryopoiesis without evidence of dysplasia or somatic mutations. One sister underwent major surgery without complications when managed with prophylactic hemostatic therapy. Their family history included multiple female relatives with similar symptoms, although formal testing was limited. Notably, none of the affected individuals developed hematologic malignancy, and only one developed esophageal cancer, with no current evidence linking this variant to solid tumors. Conclusions: This case underscores the importance of distinguishing between ANKRD26 variants when assessing malignancy risk. While ANKRD26-RT is associated with myeloid neoplasms, the c.−118C > G variant may confer a lower oncogenic potential. Variant-specific risk stratification and genetic counseling are crucial for optimizing surveillance and avoiding unnecessary interventions in low-risk individuals. Full article
Show Figures

Figure 1

13 pages, 896 KiB  
Article
Prevalence and Diversity of Staphylococcus aureus in Bulk Tank Milk from Community-Based Alpine Dairy Pastures in Tyrol, Austria
by Nasrin Ramezanigardaloud, Igor Loncaric, Patrick Mikuni-Mester, Masoumeh Alinaghi, Monika Ehling-Schulz, Johannes Lorenz Khol and Tom Grunert
Animals 2025, 15(14), 2153; https://doi.org/10.3390/ani15142153 - 21 Jul 2025
Viewed by 290
Abstract
Staphylococcus aureus frequently causes intramammary infections in dairy cows (bovine mastitis), which impair animal welfare, milk yield, and food safety. This study determined the prevalence and genetic diversity of S. aureus in bulk tank milk (BTM) samples from community-based Alpine dairy pastures in [...] Read more.
Staphylococcus aureus frequently causes intramammary infections in dairy cows (bovine mastitis), which impair animal welfare, milk yield, and food safety. This study determined the prevalence and genetic diversity of S. aureus in bulk tank milk (BTM) samples from community-based Alpine dairy pastures in Tyrol, a major milk-producing region in Austria. Throughout the 2023 Alpine season (May–September), 60.3% (94/156) of BTM samples tested positive for S. aureus at least once over the course of up to four samplings. A total of 140 isolates collected from the 94 S. aureus-positive community-based Alpine dairy pastures revealed 33 distinct spa types, with t2953 (n = 33), t529 (n = 12), t267 (n = 11), and t024 (n = 10) being the most common. Selected isolates representing the different spa types were characterised by DNA microarray-based genotyping, multi-locus sequence typing (MLST), and antimicrobial susceptibility testing. Isolates with spa types associated with bovine-adapted CC8 (CC8bov/GTB) were identified as the most common subtype, being detected in BTM samples from 35.3% (55/156) of the pastures. This emphasises the high prevalence of this subtype in dairy herds across European Alpine countries. Other common bovine-associated subtypes were also detected, including CC97, CC151, and CC479. While antimicrobial resistance was rare, enterotoxin-producing genes were detected in all CC8bov-associated spa types. Overall, these findings underscore the importance of rigorous hygiene practices in dairy farming, particularly in community-based Alpine dairy pastures, where the risk of transmission is particularly high. It also emphasises the need for continued surveillance and subtyping to improve animal health, ensure food safety, and promote sustainable milk production. Full article
(This article belongs to the Section Animal Products)
Show Figures

Figure 1

17 pages, 1342 KiB  
Review
Esophageal Squamous Papilloma and Papillomatosis: Current Evidence of HPV Involvement and Malignant Potential
by Miriana Mercurio, Roberto de Sire, Paola Campagnoli, Marco Dal Fante, Linda Fazzini, Luciano Guerra, Massimo Primignani, Maria Giuseppina Tatarella, Mauro Sollai, Sandro Ardizzone and Roberta Maselli
Cancers 2025, 17(14), 2404; https://doi.org/10.3390/cancers17142404 - 20 Jul 2025
Viewed by 536
Abstract
Human papillomavirus (HPV) is a recognized oncogenic agent in several epithelial malignancies, though its role in esophageal squamous lesions remains unclear. Esophageal squamous papilloma and papillomatosis are rare, often benign lesions, but increasing evidence suggests possible associations with high-risk HPV genotypes and a [...] Read more.
Human papillomavirus (HPV) is a recognized oncogenic agent in several epithelial malignancies, though its role in esophageal squamous lesions remains unclear. Esophageal squamous papilloma and papillomatosis are rare, often benign lesions, but increasing evidence suggests possible associations with high-risk HPV genotypes and a non-negligible risk of dysplasia and malignant transformation. This narrative review summarizes current evidence on epidemiology, clinical features, histopathology, and diagnostic approaches, emphasizing advanced endoscopic imaging techniques that improve lesion detection and characterization. Management relies primarily on complete endoscopic resection with histological and virological evaluation. While small, non-dysplastic solitary lesions may not require routine surveillance, multifocal or high-risk HPV-positive cases warrant closer follow-up. Standardized HPV testing and long-term prospective studies are needed to better define the oncogenic potential and inform surveillance and treatment strategies. Full article
(This article belongs to the Special Issue Technical Advances in Esophageal Cancer Treatment)
Show Figures

Figure 1

Back to TopTop