PURPOSE:To report a Chinese family with lattice corneal dystrophy (LCD) caused by the TGFBI p.H626R mutation and summarize its clinical and genetic characteristics through a literature review. METHODS:A three-generation Chinese family with LCD was investigated through detailed ophthalmic examination. Whole-exome sequencing followed by Sanger sequencing was performed to identify candidate variants. Bioinformatics tools were used to evaluate pathogenicity. Previously reported cases of H626R-associated LCD were reviewed. RESULTS:A heterozygous TGFBI mutation (c.1877A>G; p.His626Arg) was identified in affected individuals. All patients underwent penetrating keratoplasty at advanced stages, with improved postoperative visual acuity. A pooled analysis of 109 patients from at least 12 countries indicated that H626R-associated LCD is characterized by recurrent corneal erosions, asymmetrical progression, and thick lattice lines extending toward the corneal periphery. CONCLUSIONS:The TGFBI p.H626R mutation is associated with a distinct LCD phenotype and contributes to disease progression. Most affected individuals underwent penetrating keratoplasty at the advanced stage of the disease to restore visual acuity.
Background: Biotinidase is an enzyme recycling endogenous biotin by hydrolyzing ε- N -biotinyl lysine (biocytin) to lysine and biotin. Biotin acts as a coenzyme in various carboxylation reactions. Biotinidase deficiency is rare, with an incidence of 1 per 112,271 individuals. Objectives: Genetic characterization of a 4-month-old boy born out of a consanguineous marriage presented with cutaneous manifestations, alopecia, developmental delay, hypotonia with absent neck holding, respiratory problems, and biotinidase deficiency. Methods: Biochemical characterization was performed using tandem mass spectrometry and immunofluorescence enzyme assays. Pathogenic genetic variant was identified by Sanger sequencing of the BTD (biotinidase) gene in a patient and his parents. Results: Biochemical characterization indicated elevated methylmalonylcarnitine/hydroxyisovalerylcarnitine and decreased biotinidase, citrulline, glycine, and ornithine levels, suggesting a profound biotinidase deficiency. Sequencing of BTD gene indicates the presence of a 7-bp deletion and a 3-bp insertion (98-104del7ins3) in a homozygous state, resulting in a change of amino acid from cystine to phenylalanine at the 33rd position, causing a frameshift and premature amino acid termination at the 68th position. Conclusions: A 7-bp deletion and a 3-bp insertion (98-104del7ins3) homozygous variation in the BTD gene segregating in a homozygous recessive manner in the family, causing truncated, nonfunctional biotinidase deficiency in the proband. This is a recurrent mutation and has the potential to be used as a biomarker for screening patients with biotinidase deficiency.
BACKGROUND:Because the IL-17/IL-17 receptor (IL-17R) axis is involved in lung inflammation and genetic variants, such as single nucleotide polymorphisms (SNPs), can affect its function, this study examined the associations between IL-17/IL-17R gene SNPs, serum IL-17A levels, and community-acquired pneumonia (CAP) in Iranian children. METHODS:A total of 266 subjects were enrolled in this study, comprising 126 children with CAP and 140 healthy controls. Genetic variants in the IL-17 and IL-17R genes were characterized by allele-specific PCR and PCR restriction fragment length polymorphism, respectively. Concurrently, serum IL-17A concentrations were measured by enzyme-linked immunosorbent assay. RESULTS:Serum IL-17A levels were significantly higher in patients than in controls (295.8 ± 138.5 pg/mL vs. 40.6 ± 35.3 pg/mL, respectively; p = 0.001). Although the allele and genotype frequencies of IL-17 rs4711998 and IL-17 rs3748067 showed no significant association with CAP, the AA genotype and A allele of IL-17R rs4819554 were significantly more frequent in the patient group. Correlation analysis found no significant association between IL-17 genotypes and serum IL-17A levels. However, a significant positive correlation was observed between IL-17A levels and fever (p = 0.001). CONCLUSION:The upregulation of IL-17A in patient sera and its correlation with fever support a role for IL-17A in the pathogenesis of CAP. Furthermore, the A allele and AA genotype of IL-17R rs4819554 were identified as potential risk factors for CAP in Iranian children. The lack of a significant association between IL-17 gene variants and serum IL-17A levels may be attributable to the complex regulatory network governing IL-17 production.
Background: Glutathione-S-transferases (GSTs) play an important role in the detoxification and neutralization of oxidative stress products and xenobiotic compounds. Due to genetic polymorphisms in GST genes, GSTs partially or completely lose enzymatic activity, which may increase susceptibility to cardiovascular diseases. The objective of this study was to investigate hitherto unknown GSTM1 and GSTT1 null genotype frequencies in patients with coronary artery disease (CAD) and their potential association with CAD in the Bangladeshi population. Materials and Methods: This study included 85 patients with CAD and 56 healthy control subjects confirmed by angiogram. Clinical parameters including triglyceride (TG), cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein levels were also evaluated. Genotypes of the GSTM1 and GSTT1 genes were identified using polymerase chain reaction followed by 1.5% (W/V) agarose gel electrophoresis with subsequent detection on a UV transilluminator. Results: There were significant differences in the null genotype distribution of GSTM1 and GSTT1 alleles between controls and patients with CAD. A significant association of the null genotype with CAD susceptibility ( p < 0.05) was also observed. The combination of GSTM1 and GSTT1 null genes potentially increases the risk of CAD (odds ratio = 6.208; 95% confidence interval; p < 0.05). TG, LDL, and serum cholesterol levels were higher in patients with CAD ( p < 0.05). GSTM1 and GSTT1 null genetic variations may be associated with increased susceptibility to CAD in the Bangladeshi population. Conclusion: These findings suggest a potential association between GST gene polymorphisms and CAD susceptibility; however, larger studies are required to provide more robust and generalizable evidence in the Bangladeshi population.
OBJECTIVE:Phenylketonuria (PKU) is a genetic metabolic disorder caused by mutations in the phenylalanine hydroxylase (PAH) gene, with an incidence rate in China of approximately 1 in 11,000. PKU exhibits high heterogeneity, making the study of genotype-phenotype correlations essential for effective diagnosis and treatment. METHODS:This study aimed to analyze the genotype-phenotype correlation in pediatric PKU patients in China, with a special focus on hotspot mutations across different regions.We compared the accuracy of two prediction models: the allele phenotype value/genotype-phenotype value system and the prediction system based on the sum of assigning value (AV) scores from PAH activity, evaluating both models based on available patient data from various regions. RESULTS:The majority of genotypes in PKU patients were found to be compound heterozygotes. Classical PKU patients (cPKU) accounted for the highest proportion (44%), while the percentage of patients with mild hyperphenylalaninemia was relatively low at 22%. Among the eight regions studied, the APV/GPV system demonstrated higher accuracy (72.02%) compared with the AV score prediction system (56.82%, p < 0.05); however, for the cPKU phenotype alone, the difference in accuracy was not significant (p > 0.05). DISCUSSION:This study provides insights into the relationship between genotypes and phenotypes in PKU patients across different regions of China, emphasizing the importance of analyzing hotspot mutations for understanding genotype-phenotype correlations. The findings highlight the need to enhance hotspot mutation spectra for PKU patients and advocate for the development of more accurate prediction models, which can offer better protection for PKU patients and alleviate the burden on patients and their families.
BACKGROUND:We estimated European ancestry in U.S. Hispanics using HFE p.C282Y (c.845G > A; rs1800562), a highly informative autosomal marker of European ancestry. METHODS:We tabulated published p.C282Y allele frequencies in U.S. Hispanic control/population region/city cohorts. We assumed that Hispanics inherited p.C282Y from European ancestors only. We defined European ancestry (M) of each cohort as the quotient of its published p.C282Y frequency by the published aggregate p.C282Y frequency in Iberian Spaniards. We compared the present average region/city values of M and the aggregate M with previous European ancestries of U.S. Hispanics estimated using multiple ancestry-informative markers (AIMs). RESULTS:There were 14,472 Hispanics (nine region/city cohorts; aggregate p.C282Y frequency 0.0176 [509/28,944] [95% confidence interval: 0.0159, 0.0189]). There were 12,297 Spaniards (34 population/control cohorts; aggregate p.C282Y frequency 0.0291 (716/24,594) [0.0271, 0.0313]). Nine region/city estimates of M differed 2.6-fold: Alabama 1.0000, California/Irvine 0.5395, California/Oakland 0.6186; California/San Diego 0.9381; Connecticut 0.6873; District of Columbia 0.3883; Hawaii 0.6976; New York 0.4330; and Oregon 1.0000. The average of these nine region/city estimates of M was 0.7003. The aggregate estimate of M in the present 14,472 Hispanics was 0.6048 [0.5369, 0.6728]. The range of estimated European ancestries in 29,365 Hispanics in eight previous studies that used multiple AIMs was 0.502-0.683. CONCLUSIONS:European ancestry in U.S. Hispanics estimated using p.C282Y frequencies varies across regions/cities. The average nine region/city and aggregate European ancestry estimates in the present U.S. Hispanics are similar to those in eight previous studies that used multiple AIMs.
Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by immunodeficiency, centromeric instability, and facial dysmorphism. We report four Chinese pediatric patients with ICF syndrome diagnosed between 2018 and 2021. All patients presented with recurrent infections due to hypogammaglobulinemia. Whole-exome sequencing identified four novel mutations: CDCA7 c.695delC (p. Val233Ter), HELLS c.560T>G (p.L187W), ZBTB24 compound heterozygous (c.1228_1229delinsC and c.649_652del), and ZBTB24 homozygous (c.1208A>G, p.H403R). To our knowledge, this is the first report of CDCA7 p. Val233Ter and HELLS p.L187W mutations globally. These findings expand the mutational spectrum of ICF syndrome.
BACKGROUND:Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer, characterized by late-stage diagnosis, high metastatic potential, and recurrence. Epidermal growth factor receptor (EGFR) mutations are commonly observed in LUAD. However, other key genes associated with EGFR mutations in LUAD remain to be clarified. Therefore, this study aims to identify key genes associated with EGFR mutations in LUAD and explore their potential mechanisms. METHODS:The Cancer Genome Atlas (TCGA)-LUAD and LUAD sequencing datasets were utilized to compare survival outcomes between EGFR-mutant and wild-type groups. Differentially expressed genes (DEGs) were identified by comparing these groups within TCGA-LUAD, followed by algorithmic analysis to pinpoint key genes. Prognostic analyses were integrated with clinical features, resulting in the construction and validation of a nomogram. Further investigations included gene set enrichment analysis, tumor mutational burden evaluation, immune checkpoint profiling, immune cell infiltration analysis, and drug sensitivity testing. RESULTS:The EGFR-mutant group exhibited significantly reduced survival rates (p < 0.05); a total of 654 DEGs were identified between the EGFR-mutant group and the wild-type group. Key genes including Apolipoprotein B, C-reactive protein, kininogen 1, F2, and Alpha-2-HS-glycoprotein (AHSG) were predominantly involved in complement and coagulation cascades, ribosomal function, and cytochrome P450 metabolism. Both T and N stages were found to be independent prognostic factors and were incorporated into a highly predictive nomogram. Three immune cell types-neutrophils, activated CD4+ T cells-and five immune checkpoints were identified. Mutually exclusive and co-occurrence mutation analysis revealed a mutually exclusive relationship between Titin (TTN) and EGFR. Additionally, there were significant differences in the half-maximal inhibitory concentration values of 49 drugs between the mutant and wild groups. CONCLUSION:This study identified five key genes linked to EGFR mutations in LUAD and analyzed their clinical features, providing new perspectives for its prevention and treatment.
BACKGROUND:Coronary artery disease (CAD) is a multifactorial disorder influenced by both environmental and genetic factors. The PLAU gene, which plays a key role in fibrinolysis, inflammation, and extracellular matrix remodeling, has been implicated in atherosclerotic plaque progression. However, the relationship between PLAU polymorphisms and different clinical manifestations of CAD remains insufficiently clarified. AIMS:This study aimed to investigate the distribution of the PLAU rs2227564 polymorphism in patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS), and angiographically normal controls, and to evaluate its potential association with CAD susceptibility. METHODS:A total of 196 participants (ACS: 66, CCS: 65, controls: 65) who underwent coronary angiography were prospectively enrolled. Genotyping of the PLAU rs2227564 polymorphism was performed using real-time polymerase chain reaction with the TaqMan SNP Genotyping Assay. Genotype and allele frequencies were compared among groups. Dominant, recessive, and allelic genetic models were analyzed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. RESULTS:Overall genotype and allele distributions were similar across the study groups (p = 0.737). However, under the dominant genetic model (CT + TT vs. CC), carriers of at least one T allele showed significantly increased susceptibility to both ACS (OR: 6.84, 95% CI: 1.47-31.89, p = 0.009) and CCS (OR: 6.60, 95% CI: 1.43-30.48, p = 0.008) compared with controls. No significant associations were observed in the recessive or allelic models. CONCLUSION:Although the rs2227564 polymorphism was not independently associated with CAD based on the overall genotype distribution, the dominant model findings suggest that carrying at least one T allele may contribute to disease susceptibility in specific clinical and population contexts. These findings should be considered hypothesis-generating and require confirmation in larger multicenter studies with functional validation.
BACKGROUND:Behcet's syndrome (BS) was first described in 1937 as a triad of oral aphthae, genital ulceration, and ocular involvement. It is now recognized as a multisystemic vasculitis that can affect central nervous, gastrointestinal, and cardiovascular systems. Despite extensive research, the etiology of BS remains unclear, and genetic, viral, and environmental factors are thought to contribute to its pathogenesis. OBJECTIVE:This study aimed to investigate the role of interleukin-17 (IL-17) and IL-23 receptor (IL-23R) gene polymorphisms in the etiology of BS and to evaluate their associations with disease activity and clinical features. The IL-23/IL-17 axis was selected due to its pivotal role in T cell-mediated inflammation and vasculitis, which are key pathogenic mechanisms in BS. MATERIALS AND METHODS:This study was conducted at the Ankara University Faculty of Medicine over a 1-year period. A total of 142 patients with BS aged ≥18 years and 140 healthy controls without known rheumatologic or immunological diseases were included. BS was diagnosed according to the International Study Group criteria for Behçet's disease. Disease activity was assessed using the BS Activity Scale, and patients were classified as having active or inactive disease. Genomic DNA was extracted from peripheral blood samples. IL-17 and IL-23R gene polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS:The IL-17 rs2275913 and rs763780 polymorphisms and the IL-23R rs11209032 polymorphism were evaluated. The frequency of the homozygous AA genotype of the rs11209032 was significantly higher in the BS group than in healthy controls (85.9% vs. 17.4%, p < 0.001). Carriage of the A allele was associated with a markedly increased risk of BS; after adjustment for age and sex, carriers had approximately 16-fold higher odds of disease (adjusted odds ratios [OR] = 16.32, 95% confidence intervals [CI]: 9.76-27.12, p < 0.001). No significant differences were observed between BS patients and controls for the IL-17 polymorphisms. Gene polymorphisms were not associated with specific clinical manifestations. However, in the IL-17 rs763780 polymorphism, inactive patients had a higher frequency of the TT genotype compared with the TC genotype (p = 0.03), suggesting a potential role in disease activity rather than susceptibility. CONCLUSION:These findings suggest that IL-17 and IL-23R-related pathways may contribute to the pathogenesis of BS. While the IL-17 variant may be associated with disease activity, the IL-23R rs11209032 polymorphisms show a strong association with disease susceptibility. However, larger studies are needed to confirm these findings and clarify their clinical relevance.
BACKGROUND:It has been proposed that there is a relationship between chromosomal nondisjunction and folate metabolism. Previous studies in mothers of girls with Turner syndrome (TS) and TS patients have suggested that 5,10-methylentetrahydrofolate reductase (MTHFR) C677T and A1298C gene variants might contribute to the risk of TS. However, data in different populations have yielded contradictory results. AIM:Here, we design a case-control study to evaluate the MTHFR C677T and A1298C gene variants in TS patients and their mothers as potential risk factors for TS. MATERIALS AND METHODS:Using the TaqMan allelic discrimination assay, the frequency of the MTHFR C677T and A1298C gene variants was compared in two study groups, one of 54 girls with TS versus 93 control girls and another of 49 mothers of girls with TS versus 97 control mothers. RESULTS:The allele and genotype frequencies of the MTHFR C677T and A1298C variants were not significantly different nor showed association among TS patients compared with control girls, nor among TS mothers compared with control mothers. CONCLUSIONS:The risk of having a child with TS did not appear to be associated with the MTHFR C677T and A1298C variants in the studied population.
BACKGROUND:Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammatory disorder affecting the gastrointestinal tract. The condition's pathology not only involves the digestive system but also can impact various organs and tissues throughout the body. Metabolic syndrome is a clinical syndrome characterized by obesity, insulin resistance, hypertension, and hyperlipidemia. Extensive research suggests a potential association between IBD and metabolic syndrome. AIM:To seek biomarkers related to the diagnosis and treatment of IBD and metabolic syndrome. METHODS:In this study, we utilized bioinformatics, integrated transcriptome analysis, and machine learning to develop a diagnostic model for the co-occurrence of IBD and metabolic syndrome. We applied two machine learning algorithms to select relevant features Least Absolute Shrinkage and Selection Operator and Random Forest (RF). Moreover, through external datasets and quantitative real-time polymerase chain reaction (qRT-PCR) experiments, we validated our findings. RESULTS:We identified nine candidate gene-expression-based biomarkers (CCR6, CST7, LIMK2, TCF4, THBS3, CARS2, IFI27, LETM1, LOXL1) associated with immune and metabolic regulation that exhibited discriminatory potential for IBD complicated by metabolic syndrome. Furthermore, a column chart for diagnosing IBD in metabolic syndrome patients is provided. CONCLUSION:Our study demonstrates that integrated bioinformatics and machine learning approaches can identify transcriptomic signatures associated with IBD and metabolic syndrome, providing candidate biomarkers for further validation.
BACKGROUND:One of the multifactorial pregnancy-specific disorders that has a serious impact on maternal and perinatal morbidity is preeclampsia (PE). Long noncoding RNAs (lncRNAs), such as GAS5 and H19, have been shown in recent research to play a regulatory function in placental development and the pathophysiology of PE. AIM:To determine the diagnostic association between the lncRNAs GAS5 and H19 and PE, this study compared the expression levels of these lncRNAs in the serum of pregnant women with mild and severe PE and normotensive pregnant controls. SUBJECTS AND METHODS:A total of 195 pregnant women who visited the Obstetrics and Gynecology Department at Menoufia University Hospital between September 2023 and October 2025 participated in this case-control study. They were classified into three equal groups: normotensive pregnant women (control group, n = 65), mild PE (n = 65), and severe PE (n = 65). The levels of GAS5 and H19 expression in serum samples were assessed using quantitative real-time PCR. RESULTS:Compared with controls, both the mild and severe PE groups showed significantly higher GAS5 expression and significantly lower H19 expression. Nevertheless, there was no obvious distinction in GAS5 and H19 levels between mild and severe PE. The ROC curve analysis demonstrated that GAS5 had high sensitivity and specificity for distinguishing PE from normal pregnancy. CONCLUSION:The dysregulation of GAS5 and H19 may contribute to the pathogenesis of PE. GAS5, in particular, demonstrates promising potential as a noninvasive biomarker for PE. GAS5 and H19 do not discriminate between PE severity levels.
OBJECTIVE:To investigate the associations among protein tyrosine phosphatase (PTPN22), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) and genetic susceptibility to psoriasis in the Jiujiang population. METHODS:A total of 120 psoriasis patients and 90 healthy controls were enrolled. Polymerase chain reaction-based sequencing was performed to determine the distribution of PTPN22 rs1310182, rs2488457, and NLRP3 rs10754558 genotypes. Logistic regression analysis was conducted to evaluate the associations between the genotypes, alleles, and genetic models of these three loci and psoriasis susceptibility. The associations between these polymorphisms and disease subtypes or severity were also explored. RESULTS:With respect to the PTPN22 rs2488457 locus, the GG genotype and G allele were identified as risk factors for psoriasis susceptibility (p = 0.026 and p = 0.004, respectively). In the dominant model, carriers of the GG genotype exhibited a significantly higher risk of psoriasis than did those with the GC+CC genotype (p = 0.016). No significant associations were observed between the rs1310182 or rs10754558 polymorphisms and psoriasis susceptibility (p > 0.05). In addition, none of the three loci were significantly correlated with the disease subtype or severity (p > 0.05). CONCLUSIONS:In the Jiujiang population, the GG genotype and G allele of the PTPN22 rs2488457 locus may be key factors influencing psoriasis susceptibility.
OBJECTIVE:An epidemic of acute pneumonia caused by SARS-CoV-2 spread rapidly worldwide in December 2019. The first interaction between the virus and the host cell occurs via the binding of the spike (S) protein to the ACE2 receptor. ACE2 gene expression correlates with COVID-19 severity, and certain polymorphisms may alter expression or susceptibility. METHODS:This study investigated ACE2 rs200180615, rs149039346, rs73635825, and rs140473595 polymorphisms by PCR-RFLP. The sample included 84 controls, 80 outpatients, and 168 intensive care unit (ICU) patients. RESULTS:No significant associations were found for rs200180615, rs149039346, or rs73635825. In contrast, compared with controls, ICU patients carrying the rs140473595 CT genotype (OR = 7.222, 95% CI: 3.563-14.639, p < 0.000) or TT genotype (OR = 5.893, 95% CI: 1.578-22.000, p = 0.005) had a markedly higher risk of severe disease. Inheritance model analysis also revealed significant associations for the dominant (CC vs. CT/TT; OR = 2.37, 95% CI: 1.38-4.05) and co-dominant (CC vs. TC; OR = 2.37, 95% CI: 1.37-4.09) models. Clinical parameters including CRP, HsTroponin, D-dimer, urea, NEU, and LYM were associated with COVID-19 severity. Independent t-test analysis showed that mutant allele carriers (CT, TT) had significant alterations in these parameters compared with the wild-type CC genotype, consistent with trends observed as disease severity increased. CONCLUSION:The ACE2 rs140473595 polymorphism is associated with COVID-19 severity. Broader studies in diverse populations are needed to further clarify the role of ACE2 variants in disease progression.
BACKGROUND:Incurable hereditary diseases such as Duchenne muscular dystrophy (DMD), Huntington's disease (HD), and myotonic dystrophy type 1 (DM1) fall into the nucleotide repeat expansion disorder (NRED) category. The discovery of CRISPR-Cas genome editing has paved the way toward hopeful strategies for accurate DNA-level repair. This systematic review presents preclinical data on the efficacy, molecular effects, and limitations of CRISPR-based treatments for NREDs. METHODS:As per Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, systematic PubMed, Scopus, and Embase searches up to June 2025 identified studies that evaluated CRISPR-Cas systems in human-derived in vitro models of NREDs. Methodological Index for Non-Randomized Studies tool was used to score eligible studies by methodological quality. CRISPR platforms, delivery systems, gene targets, molecular endpoints, and functional rescue data were extracted and synthesized descriptively. RESULTS:Twenty-four out of 6510 records screened were included. They employed most of them to target specific DMD (n = 9), HD (n = 6), and DM1 (n = 3) with patient-derived induced pluripotent stem cells or differentiated myogenic/neuronal cells. Streptococcus pyogenes CRISPR-associated protein 9 as a nuclease was the most frequently used, although engineered Cas9 enzymes and dCas9 fusion proteins were also utilized to control transcription. Delivery was achieved through viral vectors (adeno-associated virus, lentivirus) and nonviral routes (plasmid, lipofection, electroporation). Uniform genomic editing, transcript rescue, and protein restoration were seen in CRISPR-mediated editing studies, and functional restoration was demonstrated for splicing correction and dystrophin restoration. Methodological flaws such as the absence of blinding, failure to follow up, and lack of full reporting of off-target effects limited robustness. CONCLUSION:CRISPR-Cas systems exhibit reproducible molecular and functional correction in NRED models with their translational potential. Methodological strength, whole safety profiling, and in vivo verification remain a necessity, however, before clinical translation.
BACKGROUND AND AIMS:Family with sequence similarity 216 member A (FAM216A) is overexpressed in several cancer tissues, but its prognostic value and pathological effect in hepatocellular carcinoma (HCC) have not been fully elucidated. MATERIALS AND METHODS:FAM216A expression in HCC specimens and cell lines was determined by real-time PCR and western blotting. FAM216A expression was knocked down in HCCLM3 and Huh7 cells, and overexpressed in Hep3B and PLC/PRF/5 cells. The proliferation, migration, and invasion of different HCC cell lines were assessed by colony formation and Transwell assays. The expression of epithelial-mesenchymal transition (EMT)-related proteins and the level of polo-like kinase 1/extracellular regulated protein kinase (PLK1/ERK) were determined. RESULTS:Increased FAM216A expression was observed in HCC tissues, a result that is consistent with outcomes obtained from an online database, and patient prognosis was negatively correlated with the FAM216A expression level. Additionally, FAM216A overexpression promoted the proliferation, migration, and invasion of HCC cells and activated EMT via the PLK1/ERK signaling pathway. CONCLUSIONS:FAM216A is overexpressed in HCC tissues and is associated with poor clinical outcomes. Mechanistically, FAM216A promotes aggressive tumor behavior by activating the PLK1/ERK signaling pathway.
BACKGROUND:X-linked female-limited high myopia (MYP26, OMIM:301010) is a rare Mendelian subtype of early-onset high myopia (eoHM), with females having progressive myopic refractive error (≥-6 D) and males as asymptomatic carriers. Pathogenic variants in ARR3 (OMIM:301770) have been linked to eoHM, but the spectrum of ARR3 variants in Chinese populations remains incompletely defined. OBJECTIVE:To identify the causative variant in a Chinese eoHM family and expand ARR3 variant spectrum for MYP26. METHODS:We conducted clinical and genetic analyses of a Chinese family with eoHM. The proband underwent clinical examinations and whole-exome sequencing (WES). Sanger sequencing validated variants in affected family members, and bioinformatics tools evaluated variant pathogenicity. RESULTS:WES identified an ARR3 c.214C>T (p.R72X) stop-gain variant, co-segregating with the disease phenotype and predicted to truncate cone arrestin, disrupting phototransduction. A female carrier showing incomplete penetrance (I-1) was identified, which highlights the unrecognized complexity of the pathogenic mechanism underlying MYP26. This variant was first reported in the Chinese population. CONCLUSIONS:Our study expands the ARR3 variant spectrum associated with eoHM, highlighting the role of ARR3 c.214C>T (p.R72X), first reported in Chinese populations. The finding of incomplete penetrance underscores the complexity of X-linked female-limited inheritance and provides a reference for genetic counseling of related families.
Red blood cell (RBC) membranopathies, caused by genetic alterations in membrane and cytoskeletal proteins, lead to significant variability in clinical presentation. This study analyzes 23 single nucleotide variants across nine genes (ADD1, ADD2, ANK1, EPB41, PIEZO1, SLC4A1, SPTA1, SPTB, and TAF3) in 225 Mexican patients with suspected RBC membranopathies and their effects on hematological parameters. Key variants, such as ADD2:c.1797C>T, SPTA1:c.5992G>C, SPTA1:c.6046C>A and SPTA1:c.6531-12C>T, were significantly associated with decreased RBC count, hemoglobin levels, packed cell volume, mean corpuscular hemoglobin and/or mean corpuscular hemoglobin concentration. Additionally, the following six combinations showed significant associations with two or three hematological parameters: SPTA1:c.5992G>C + SPTA1:c.6046C>A, SPTA1:c.5992G>C + ADD1:c.1378G>T, ADD1:c.1378G>T + ADD2:c.1797C>T, ADD1:c.1378G>T + PIEZO1:c.6793A>G, ADD2:c.1797C>T + PIEZO1:c.6793A>G, and TAF3:c.410-2550A>G + SPTA1:c.6531-12C>T. These findings underscore the importance of selected population genetic studies to increase our understanding of genotype-hematological phenotype relationships in RBC membranopathies.
OBJECTIVE:Major depressive disorder (MDD) is a prevalent and disabling psychiatric condition in Saudi Arabia, with genetic susceptibility remaining incompletely characterized. Reduced brain-derived neurotrophic factor (BDNF) activity has been implicated in MDD. The Val66Met polymorphism (rs6265), involving the substitution of valine (Val, G allele) with methionine (Met, A allele), impairs activity-dependent BDNF secretion. This study examined the frequency of Val66Met and its association with MDD in a Saudi cohort. MATERIALS AND METHODS:A case-control study was conducted, including 87 patients with MDD (44 males, 43 females; mean age 44.2 ± 11.5 years) and 87 healthy controls (39 males, 48 females; mean age 28.7 ± 8.4 years). Genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction. Unadjusted and age- and sex-adjusted logistic regression analyses were applied under genotype-specific, dominant, recessive, and allelic models. RESULTS:The Val/Val (GG) genotype was more frequent in controls than patients (54.0% vs. 34.5%), whereas the Met/Met (AA) genotype was detected exclusively in patients (21.8% vs. 0%; χ2 = 22.80, p = 1.1 × 10-5). The Met (A) allele frequency was significantly higher in patients (43.7% vs. 23.0%; χ2 = 15.84, p = 6.9 × 10-5). Unadjusted analysis showed a protective effect of GG (OR = 0.45, 95% CI: 0.24-0.82) and a markedly increased risk associated with AA (OR = 49.81, 95% CI: 2.95-839.90). Dominant carriers (GA + AA) had increased odds of MDD (OR = 2.23), and each A allele conferred a higher risk (OR = 2.60). These associations remained significant after adjustment for age and sex. CONCLUSION:The BDNF Val66Met polymorphism is associated with MDD susceptibility in Saudis. The Met (A) allele, particularly in homozygosity, confers increased risk, while the Val/Val genotype appears protective, supporting population-specific genetic contributions to depression.
