Search Results (3,897)

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

Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus s.s. was evaluated using 46 hydatid cyst samples obtained from sheep, goats, cattle, and humans across three regions of Chile: Coquimbo, La Araucanía, and Magallanes. Mitochondrial cox1 gene sequences were analyzed and compared with reference sequences reported from South America, Europe, Africa, Asia, and Oceania. In Chile, the EG01 haplotype was the predominant haplotype. A total of four haplotypes were identified, with low haplotype diversity (Hd = 0.461 ± 0.00637) and low nucleotide diversity (π = 0.00181 ± 0.00036). The haplotype network displayed a star-like configuration, with the EG01 genotype at the center, suggesting a potentially ancestral or widely distributed lineage. In Coquimbo (Tajima’s D = −0.93302, p = 0.061; Fu’s Fs = −0.003, p = 0.502) and Magallanes (Tajima’s D = −0.17406, p = 0.386; Fu’s Fs = −0.121, p = 0.414), both neutrality tests were non-significant, indicating no strong evidence for recent population expansion or selection. Star-like haplotype network patterns were also observed in populations from Europe, the Middle East, Asia, Africa, and Oceania, with the EG01 genotype occupying the central position. The population genetic structure of Echinococcus granulosus s.s. in Chile demonstrates considerable complexity, with EG01 as the predominant haplotype. Further comprehensive studies are required to assess the intraspecific genetic variability of E. granulosus s.s. throughout Chile and to determine whether this variability influences the key biological traits of the parasite. This structure may prove even more complex when longer fragments are analyzed, which could allow for the detection of finer-scale microdiversity among isolates from different hosts. We recommended that future cystic echinococcosis control programs take into account the genetic variability of E. granulosus s.s. strains circulating in each endemic region, to better understand their epidemiological, immunological, and possibly pathological differences. Full article

Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is to evaluate the association between CYP7A1, NR1H1, RXRA, and PPARA gene variants and risk of ICP. Five single nucleotide variants (SNVs), rs3808607 (CYP7A1), rs56163822 (NR1H4), rs1800206 (PPARA), rs749759, and rs11381416 (NR2B1), were genotyped in a group of 96 ICP and 211 controls. The T allele of the CYP7A1 (rs3808607) variant may be a protective factor against ICP risk (OR = 0.697, 95% CI: 0.495–0.981, p = 0.038). Genetic model analysis showed that rs3808607 was associated with decreased risk of ICP under dominant (OR = 0.55, 95% CI: 0.32–3.16, p = 0.032, AIC = 380.9) and log-additive models (OR = 0.71, 95% CI: 0.51–1.00, p = 0.046, AIC = 381.4). The A insertion in the rs11381416 NR2B1 variant was associated with the degree of elevation in the liver function tests TBA (34.3 vs. 18.8 μmol/L, p = 0.002), ALT (397.0 vs. 213.0 IU/L, p = 0.017), and AST (186.0 vs. 114.4 IU/L, p = 0.032) in ICP women. Results indicate an association between the CYP7A1 rs3808607 and the risk of ICP and the association of the rs11381416 of the NR2B1 receptor with higher values of liver function tests in women with ICP. A better understanding of the cooperation of proteins involved in BA metabolism may have important therapeutic implications in ICP and other hepatobiliary diseases. Full article

Cervical cancer remains a major health burden among women in sub-Saharan Africa, where screening is often limited. Persistent high-risk human papillomavirus (HR-HPV) infection is the principal cause, highlighting the need for accurate molecular diagnostics. This cross-sectional study evaluated the analytical performance of one mRNA assay, APTIMA^® HPV assay (APTIMA mRNA), and two DNA-based assays, the Abbott RealTime High Risk HPV assay (Abbott DNA) and Seegene Allplex™ II HPV28 assay (Seegene DNA), in 527 cervical samples from a South African tertiary hospital, focusing on 14 shared HR-HPV genotypes. Seegene DNA yielded the highest detection rate (53.7%), followed by Abbott DNA (48.2%) and APTIMA mRNA (45.2%). APTIMA mRNA showed a strong agreement with Abbott DNA (87.9%, κ = 0.80), 89.9% sensitivity, 91.2% NPV, and the highest accuracy (AUC = 0.8804 vs. 0.8681). The agreement between APTIMA mRNA and Seegene DNA was moderate (83.4%, κ = 0.70), reflecting target differences. Many DNA-positive/mRNA-negative cases likely represent transient infections, though some may be latent with reactivation potential, warranting a follow-up. In resource-constrained settings, prioritizing transcriptionally active infections through mRNA testing may enhance screening efficiency and reduce burden. Scalable, cost-effective assays with strong clinical utility are essential for broadening access and improving cervical cancer prevention. Further studies should assess the integration of mRNA testing into longitudinal screening algorithms. Full article

Background/Objectives: Variations in hair length are observed in many dog breeds, as determined by the canine FGF5 gene. Long-haired Akitas, which are disqualified under breeding standards of Akitas, are sometimes born to short-haired parents and may have been subjected to treatments compromising animal welfare. Here, we aimed to identify an FGF5 variant associated with hair coat variations in Akitas in Japan, and to assess how welfare of this breed can be improved by carefully planned breeding. Methods: DNA samples were obtained from 60 Akitas in 2021 (modern Akitas) and 73 Akitas in the 1970s and the 1980s (classic Akitas). Sanger sequencing was performed on all exons and exon–intron junctions of the FGF5 gene to determine the causative variant of long hair in Akitas. A real-time PCR assay was developed to genotype FGF5:c.578C>T in modern and classic Akitas. Using 54 dogs from modern Akitas, scores (1 to 10) of hair length were compared among the three genotypes (C/C, C/T, and T/T). Results: Sanger sequencing revealed that the canine FGF5:c.578C>T variant was associated with long hair in Akitas in Japan. Genotyping revealed that the frequency of the mutant T allele was 0.350 in modern Akitas, which was significantly higher (p < 0.001) than in classic Akitas (0.212). The three genotypes were not in Hardy–Weinberg equilibrium (HWE) in modern Akitas but were in HWE in classic Akitas. There were significant differences in hair length scores among the three genotypes (p < 0.001) and between the C/C and C/T genotypes (p < 0.005). There was no significant difference in the scores between male and female dogs. Conclusions: This study revealed that a causative variant that determines the long hair trait of Akitas in Japan was the FGF5:c.578C>T variant, which was inherited in an incompletely dominant manner. Akita dog breeders were more likely to select heterozygous C/T dogs based on the appearance of the hair coat for breeding dogs with an ideal fluffy hair coat. This might result in a high mutant T allele frequency and the production of undesired long-haired Akitas with T/T, which may create welfare problems. Genetic testing for this variant is necessary to improve welfare and conserve the Akita breed. Full article

Background/Objetives: Antimicrobial Resistance (AMR) is a multifaceted issue that the World Health Organization (WHO) identifies as one of the primary threats to global health for humans, animals, and the environment. In Colombia, AMR has been extensively studied at the hospital level; however, there are limited environmental studies, particularly concerning leachates from landfills. The objective of this study was to identify and determine the genetic relationships, as well as the sensitivity profiles to antibiotics and heavy metals, of ten Pseudomonas mendocina isolates from a leachate pond. Methods: Identification was conducted using MALDI-TOF (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight), while genotyping was performed via rep-PCR. Antibiotic susceptibility to β-lactams, aminoglycosides, and quinolones was assessed using the Kirby-Bauer method. Additionally, sensitivity profile to heavy metals was evaluated using the broth microdilution technique. Results: Rep-PCR analysis indicated that 60% (n = 6/10) of the isolates exhibited a clonal relationship. Sensitivity testing revealed that 30% (n = 3/10) of the isolates displayed reduced sensitivity to aminoglycosides and β-lactams. Finally, the broth microdilution showed that 90% (n = 9/10) of the isolates were tolerant to copper sulfate. Conclusions: These results provide evidence that landfill leachates may serve as a potential reservoir for bacteria harboring antimicrobial resistance determinants. Full article

Hepatocellular carcinoma (HCC) is the most prevalent subtype of liver cancer with an increasing incidence worldwide. Single nucleotide polymorphisms (SNPs) may influence disease risk and serve as predictive markers. This study aimed to evaluate the association of PNPLA3 (rs738409 and rs2294918), GCKR (rs780094), MBOAT7 (rs641738), NCAN (rs2228603), and TM6SF2 (rs58542926) SNPs with the risk of developing HCC in a Mexican population. A case-control study was conducted in unrelated Mexican individuals. Cases were 173 adults with biopsy-confirmed HCC and 346 were healthy controls. Genotyping was performed using TaqMan allelic discrimination assay. Logistic regression was applied to evaluate associations under codominant, dominant, and recessive inheritance models. p-values were corrected using the Bonferroni test (pC). Haplotype and gene–gene interaction were also analyzed. The GG homozygous of rs738409 and rs2294918 of PNPLA3, TT, and TC genotypes of GCKR, as well as the TT genotype of MBOAT7, were associated with a significant increased risk to HCC under different inheritance models (~Two folds in all cases). The genotypes of NCAN and TM6SF2 did not show differences. The haplotype G-G of rs738409 and rs2294918 of PNPLA3 was associated with an increased risk of HCC [OR (95% CI) = 2.2 (1.7–2.9)]. There was a significant gene–gene interaction between PNPLA3 (rs738409), GCKR (rs780094), and MBOAT7 (rs641738) (Cross-validation consistency (CVC): 10/10; Testing accuracy = 0.6084). This study demonstrates for the first time that PNPLA3 (rs738409 and rs2294918), GCKR (rs780094), and MBOAT7 (rs641738) are associated with an increased risk of developing HCC from multiple etiologies in Mexican patients. Full article

Coffee beverage quality is determined by a complex interaction of genetic and environmental factors, including specific biochemical characteristics. In this context, the present study aimed to estimate the genetic parameters of elite irrigated Conilon coffee genotypes in the Cerrado over two consecutive years based on the biochemical characteristics of the beans, assessed by near-infrared spectroscopy (NIRS). The research was conducted at the Embrapa Cerrados experimental field, using the unit’s elite collection. Levels of chlorogenic acid (5-ACQ), caffeine, sucrose, citric acid and trigonelline were analyzed in the raw beans of 18 genotypes harvested in two consecutive years. Data were subjected to analysis of variance in a time-subdivided plot design, considering genotypes as plots and years as subplots, with means grouped by the Scott-Knott test at 5% significance. Results showed significant genetic variability for caffeine, sucrose and trigonelline, while chlorogenic and citric acid levels did not differ significantly among genotypes. A significant genotype × year interaction was observed for caffeine, sucrose, and 5-ACQ. Estimated heritabilities were high for caffeine (85.5%), trigonelline (80.1%), sucrose (62%) and citric acid (60%). Selection gains were positive for sucrose (5.58%), citric acid (10.01%) and trigonelline (8.27%), and negative for caffeine (−6.87%) and 5-ACQ (−0.47%). It is concluded that among the compounds evaluated, caffeine shows the greatest potential for selection, enabling effective gains in raw bean composition, while sucrose and trigonelline present moderate potential for genetic improvement. Full article

This study investigates the effects of low nitrogen (N) and phosphorus (P) stress on the growth and yield of nine barley (Hordeum vulgare L.) genotypes (1267-2, 1749-1, 1149-3, 2017Y-2, 2017Y-16, 2017Y-17, 2017Y-18, 2017Y-19, and XBZ17-1-61), all of which are spring two-rowed hulled barley types from the Economic Crops and Beer Material Institute, Gansu Academy of Agricultural Sciences. Data were collected over two consecutive growing seasons (2021–2022) at Huangyang Town (altitude 1766 m, irrigated desert soil with 1.71% organic matter, 1.00 g·kg⁻¹ total N, 0.87 g·kg⁻¹ total P in 0–20 cm plough layer) to elucidate the correlation between stress tolerance traits and yield performance. Field experiments were conducted under two treatment conditions: no fertilization (NP0) and normal fertilization (180 kg·hm⁻² N and P, NP180). Growth indicators (plant height, spike length, spikelets per unit area, etc.) and quality indicators (proportion of plump/shrunken grains, 1000-grain weight, protein, starch content) were measured, and data were analyzed using correlation analysis, principal component analysis, and structural equation modeling. The results revealed that low N and P stress significantly impacted quality indicators, such as the proportion of plump and shrunken grains, while having a minimal effect on growth indicators like plant height and spike length. Notably, the number of spikelets per unit area emerged as a critical factor positively influencing yield. Among the tested genotypes, 1749-1, 1267-2, 1149-3, 2017Y-16, 2017Y-18, 2017Y-19, and XBZ17-1-61 exhibited superior yield performance under low N and P stress conditions, indicating their potential for breeding programs focused on stress resilience. Included among these, the 1749-1 line showed the best overall performance and consistent results across both years. Full article

The occurrence of PCV2 genotypes in domestic pig production is a dynamic process that undergoes continuous change. Beginning with PCV2a as the first recognized genotype, PCV2b, and subsequently PCV2d, has become the most prevalent one over time. The present study provides an update on the prevalence of the three major PCV2 genotypes in Germany in 2024. A total of 87 fattening farms were randomly selected, proportionally based on farm density within the respective federal states. On each farm, oral fluid samples (OFs) were collected from approximately 100 pigs aged 18 (±1) weeks. Oral fluids (OFs) were pooled and screened for PCV2 DNA by qPCR. Positive samples were subsequently examined by genotype specific qPCR. In total, 31.0% (27/87) of all farms were identified as PCV2-positive. PCV2a was detected in 8.0% (7/87) of farms, while 3.4% (3/87) tested positive for both PCV2a and PCV2d. Overall, 11.5% (10/87) of all farms were PCV2d-positive. No significant effect of vaccination status of the pigs on the viral load or frequency of detection of PCV2 DNA was detected. Full article

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

Game-farmed quails that are currently raised in captivity and released in hunting preserves are not attractive for many hunters because of their low antipredator instinct, which is due to the fact that in most cases, these farm-reared quails are hybrids between European common (Coturnix coturnix) and Japanese (Coturnix japonica) quails, with the latter having been selectively bred for docility. This study aimed at assessing the antipredator response of game-farmed and Japanese quails by performing three tests: human approach test, simulated aerial predator approach test and tonic immobility test. Thirty game-farmed quails (average body weight: 133 g) and thirty Japanese quails (323 g) were subjected to the tests. For each genotype of quail, fifteen males and fifteen females were used. In the human approach test, the distance at which quails moved was greater for game-farmed quails than for Japanese ones (37.4 vs. 19.6 m, p < 0.001). In the simulated aerial predator approach test, female quails of the Japanese species crouched down at the longest distance with respect to the predator (9.83 m), whereas no significant difference existed for this trait among the other three groups (6.84 m, on average). The percentage of quails flying when the predator got closer was higher for the Japanese species than for the game-farmed quails (23.3 vs. 3.33%, p = 0.023). Fewer inductions were needed to cause tonic immobility in the game-farmed quails than in the Japanese ones (3.10 vs. 4.10, p = 0.009), but then, the duration of the tonic immobility response did not differ significantly between the two genotypes. No effect of sex was detected in the human approach and tonic immobility tests. In conclusion, as compared with Japanese quails, game-farmed quails showed more fearful behaviour when confronted with a human being. Full article

Background: Lysosomal storage diseases (LSDs) are a genetically and clinically heterogeneous group of inborn errors of metabolism caused by variants in genes encoding lysosomal hydrolases, membrane proteins, activator proteins, or transporters. These disease-causing variants lead to enzymatic deficiencies and the progressive accumulation of undegraded substrates within lysosomes, disrupting cellular function across multiple organ systems. While classical phenotypes typically manifest in infancy or early childhood with severe multisystem involvement, a combination of advances in molecular diagnostics [particularly next-generation sequencing (NGS)] and improved understanding of disease heterogeneity have enabled the identification of attenuated forms characterised by residual enzyme activity and later-onset presentations. These milder phenotypes often evade early recognition due to nonspecific or isolated symptoms, resulting in significant diagnostic delays and missed therapeutic opportunities. Objectives/Methods: This study characterises the clinical, biochemical, and molecular profiles of 10 adult patients diagnosed with LSDs, all representing attenuated forms, and discusses them alongside a narrative review. Results: Enzyme activity, molecular data, and phenotypic assessments are described to explore genotype–phenotype correlations and identify diagnostic challenges. Conclusions: These findings highlight the variable expressivity and organ involvement of attenuated LSDs and reinforce the importance of maintaining clinical suspicion in adults presenting with unexplained cardiovascular, neurological, ophthalmological, or musculoskeletal findings. Enhanced recognition of atypical presentations is critical to facilitate earlier diagnosis, guide management, and enable cascade testing for at-risk family members. Full article

Background/Objectives: Impulsivity is a key psychological construct implicated in the onset and maintenance of behavioural addictions. Dysregulation of impulsivity is central to behavioural addictions, yet its genetic basis remains unclear. This study examined the association between the DAT1 variable number tandem repeat polymorphism and impulsivity in individuals with behavioural addictions. Methods: A total of 328 males (128 with behavioural addictions and 200 controls) completed the Barratt Impulsiveness Scale. DAT1 genotyping was performed via PCR and gel electrophoresis. Statistical analyses included chi-square tests, Mann–Whitney U-tests, and two-way ANOVA. Results: No differences in DAT1 genotype frequencies were found between groups. However, a significant interaction emerged for attentional impulsivity: individuals with behavioural addictions and the 9/9 genotype had the highest BIS-AI scores (F_{2, 322} = 5.48; p = 0.0046). Conclusions: The DAT1 9/9 genotype may increase vulnerability to attentional impulsivity, but only in the context of behavioural addictions. These findings highlight a gene–environment interaction and support the role of dopaminergic mechanisms in cognitive dysregulation. Future studies should validate these findings using longitudinal designs and neurobiological methods. Full article

Background: Effective triage of women testing positive for high-risk HPV DNA is essential to reduce unnecessary colposcopies while preserving cancer prevention. Cytology, the current standard, has limited specificity and reproducibility. The genotype-specific 7-type HPV E6/E7 mRNA test (PreTect HPV-Proofer’7), targeting HPV types 16, 18, 31, 33, 45, 52, and 58, detects transcriptionally active infections and may enhance risk stratification. Methods: Between 2019 and 2023, 34,721 women aged 25–69 underwent primary HPV DNA screening with the Cobas 4800 assay at the University Hospital of North Norway, within the national screening program. Of these, 1896 HPV DNA-positive women were triaged with liquid-based cytology with atypical squamous cells of undetermined significance or worse (≥ASC-US) and the 7-type HPV mRNA test. Histological outcomes were followed through October 2024. Diagnostic performance for CIN2+ was evaluated overall and by genotype. Results: CIN2+ prevalence was 13.3%. The mRNA test reduced test positivity from 50.3% to 33.4% while maintaining comparable sensitivity (70.6% vs. 72.2%) and improving specificity (72.3% vs. 53.0%) and PPV (28.1% vs. 19.1%). Genotype-specific PPVs were highest for HPV16 mRNA (47.7%), followed by HPV33 (39.2%) and HPV31 (32.2%), all exceeding corresponding DNA-based estimates. Conclusion: Genotype-specific HPV mRNA triage offers superior risk discrimination compared to cytology, supporting more targeted, efficient, and accessible cervical cancer screening. Full article