Specific Variants Research Articles

Asymptomatic pediatric presentation of S‐adenosylhomocysteine hydrolase deficiency

AbstractS‐adenosylhomocysteine hydrolase deficiency is an autosomal recessive inborn error of metabolism affecting methylation by disrupting the methionine cycle. Its clinical spectrum spans from severe perinatal encephalomyopathy and liver failure to asymptomatic course in patients with isolated hypermethioninemia. We present two new cases of S‐adenosylhomocysteine hydrolase deficiency from Pakistani origin clinically asymptomatic at presentation. Both siblings showed mild chronic liver failure and elevation of creatine kinase. The older patient presented at 6 years of age with isolated verbal processing difficulty and mild diffuse leukodystrophy, reversible 12 months after introduction of methionine dietary restriction. The patient showed subtle atrophy in the muscle MRI at the age of 7 years. S‐adenosylhomocysteine hydrolase deficiency was confirmed with homozygous missense variant c.146G>A (p.Arg49His) in the AHCY gene, a genotype previously reported in Pakistani patients with mild presentation. Dietary methionine restriction decreased plasma methionine but not plasma S‐adenosylhomocysteine and S‐adenosylmethionine. This work expands the mild spectrum of S‐adenosylhomocysteine hydrolase deficiency with no noticeable clinical symptoms in children, highlighting a specific hotspot variant from South Asia. This mild form of the disease is likely underdiagnosed and raises the question of therapeutic management to prevent long‐term complications documented in the literature, such as hepatocellular carcinoma and myopathy in early adulthood.

Epidemiological, Clinical and Biological Profile of O Arab Hemoglobinosis: Experience of the Biochemistry Toxicology Department of HMIMV

Background: Hemoglobinopathies (HbPs) are inherited disorders of red blood cells caused by abnormalities in the globin chains of hemoglobin (Hb). Hemoglobin O-Arab is a specific variant with a mutation in the β-chain. These disorders range from asymptomatic to severe and represent a significant public health issue. Methods: A retrospective study was conducted over 10 years (February 2014 to April 2024) in the Biochemistry-Toxicology Department of HMIMV in Rabat. Hemoglobin variants were detected using HPLC and capillary electrophoresis. Data on socio-epidemiological, clinical, and biological aspects were collected from patient follow-up forms. Results: of 17,843 hemoglobin studies, 1,154 hemoglobinopathies (5.4%) were identified, with 63 cases (0.35%) of hemoglobin O-Arab: 58 heterozygous, 4 homozygous, and 1 composite heterozygous. Most cases were detected incidentally during HbA1c testing. Homozygous cases showed anemia, while heterozygous cases showed no significant abnormalities. The composite heterozygous case had severe clinical complication. Conclusions: Hemoglobinopathies, including hemoglobin O-Arab, are common genetic disorders. Advanced diagnostic techniques like capillary electrophoresis have improved detection, but multiple methods are still needed for accurate diagnosis. Effective collaboration between clinicians and laboratories is crucial for managing these disorders.

Serum oxidative stressors levels and association of mtDNA variants with type 2 diabetes mellitus in the Central India population

BackgroundThe mitochondrial genome has a high rate of mutability which plays a major role in pathogenic mutations. These mutations are implicated with mitochondrial dysfunction increasing the vulnerability to Diabetes Mellitus (DM). AimThe study aimed to evaluate the changes in oxidative markers and analyse the specific mitochondrial DNA variants that contributed to DM in the central Indian population. MethodTo assess mitogenomic alteration, Sanger sequencing was used to identify the single nucleotide polymorphisms (SNPs) or variants, while ELISA kits were used to evaluate oxidative stress. ResultsThe levels of 8-Hydroxy-2-deoxyguanosine (8-OHdG) and Malondialdehyde (MDA) in type 2 diabetes mellitus (T2DM) were significantly higher than in healthy individual (HI). In T2DM (3371.80 ± 1110.7 pg/ml) the levels of 8-OHdG were significantly greater and were found to be nine times higher compared to the control group (P < 0.001). Additionally, MDA level which is indicative of lipid peroxidation, in the diabetic groups (39.34 ± 23.05 ng/ml) contributed to 18 times higher than the control groups (2.16 ± 2 ng/ml). Moreover, 52 variants were found in our population, among which C10400T variants were significantly prevalent and clustered with the A10398G. These variants confirmed a strong association, on analysis for linkage disequilibrium (r2), with a slightly higher r2 value in the T2DM group (0.92) compared to controls (0.85), indicating a stronger link with diabetes. According to multivariate regression analysis, variants associated with the mitogenome such as C16192T (CI: 0.004 to 1.30, p = 0.028) were found to play a protective role against T2DM. Furthermore, A3384G and G16129A may contribute to the protective role against the risk of developing diabetes. ConclusionThe study demonstrates that diabetic patients are more vulnerable to certain mtDNA variants, directly linked to increased hyperglycemia. Elevated free radical-mediated oxidative stress likely affects these mtDNA variants.

A novel role of ETV6 as a pro-viral factor in host response by inhibiting TBK1 phosphorylation

E26-transforming specific (ETS) variant 6 (ETV6) is a transcription factor regulating the expression of interferon stimulating genes (ISGs) and involved in the embryonic development and hematopoietic regulation, but the role of ETV6 in host response to virus infection is not clear. In this study, we show that ETV6 was upregulated in DF-1 cells with poly(I:C) stimulation or IBDV, AIV and ARV infection via engagement of dsRNA by MDA5. Overexpression of ETV6 in DF-1 cells markedly inhibited IBDV-induced type I interferon (IFN-I) and ISGs expressions. In contrast, knockdown, or knockout of ETV6 remarkably inhibited IBDV replication via promoting IFN-I response. Furthermore, our data show that ETV6 negatively regulated host antiviral response to IBDV infection by interaction with TANK binding kinase 1 (TBK1) and subsequently inhibited its phosphorylation. These results uncovered a novel role of ETV6 as a pro-viral factor in host response by inhibiting TBK1 phosphorylation, furthering our understandings of RNA virus immunosuppression and providing a valuable clue to the development of antiviral reagents for the control of avian RNA virus infection.

Genomic insights into mRNA COVID-19 vaccines efficacy: Linking genetic polymorphisms to waning immunity

ABSTRACT Genetic polymorphisms have been linked to the differential waning of vaccine-induced immunity against COVID-19 following vaccination. Despite this, evidence on the mechanisms behind this waning and its implications for vaccination policy remains limited. We hypothesize that specific gene variants may modulate the development of vaccine-initiated immunity, leading to impaired immune function. This study investigates genetic determinants influencing the sustainability of immunity post-mRNA vaccination through a genome-wide association study (GWAS). Utilizing a hospital-based, test negative case-control design, we enrolled 1,119 participants from the Taiwan Precision Medicine Initiative (TPMI) cohort, all of whom completed a full mRNA COVID-19 vaccination regimen and underwent PCR testing during the Omicron outbreak. Participants were classified into breakthrough and protected groups based on PCR results. Genetic samples were analyzed using SNP arrays with rigorous quality control. Cox regression identified significant single nucleotide polymorphisms (SNPs) associated with breakthrough infections, affecting 743 genes involved in processes such as antigenic protein translation, B cell activation, and T cell function. Key genes identified include CD247, TRPV1, MYH9, CCL16, and RPTOR, which are vital for immune responses. Polygenic risk score (PRS) analysis revealed that individuals with higher PRS are at greater risk of breakthrough infections post-vaccination, demonstrating a high predictability (AUC = 0.787) in validating population. This finding confirms the significant influence of genetic variations on the durability of immune responses and vaccine effectiveness. This study highlights the importance of considering genetic polymorphisms in evaluating vaccine-induced immunity and proposes potential personalized vaccination strategies by tailoring regimens to individual genetic profiles.

Pediatric Epilepsy Genetic Testing Results and Long-term Seizure Freedom.

Objective: To determine whether there is a correlation of genetic diagnosis/result with long-term seizure freedom in pediatric epilepsy patients. Methods: This was a prospective and retrospective cohort study of children with epilepsy referred for genetic testing at a single center. The primary outcomes were presence and type of genetic diagnosis (pathogenic, benign, or variant of uncertain significance) and patient epilepsy status (seizure free, treatment failure, uncertain). Epilepsy gene panels were the primary method of genetic testing. Results: The prospective cohort had 22 patients followed for >11 years and for whom genetic testing was then performed; the retrospective cohort had 78 patients with previous genetic testing followed for >8 years. In the prospective cohort, one patient each of the seizure free or treatment failure groups had a pathogenic genetic variant; mean Combined Annotation Dependent Depletion (CADD) scores 22 and 24, respectively (P = .62). In the retrospective cohort, there was no difference in the number of variants (P = .97), the variant interpretations (P = .29 ClinVar, P = .39 lab interpretation) or mean CADD scores (P = .29) between the seizure-free, treatment failure, and uncertain epilepsy patients. Whole exome and genome sequencing identified pathogenic variants in 70% of patients with treatment failure but were not performed in seizure-free patients. Significance: Our findings show no correlation of the presence or type of epilepsy gene panel result with long-term seizure freedom in pediatric patients. The yield and specificity of pathogenic variants may be higher using whole exome and whole genome sequencing in patients with treatment-resistant epilepsy. Whole exome and whole genome sequencing, or more targeted understanding of specific variants, may be needed to improve the utility of pediatric epilepsy genetic testing.

Exploring the Role of the TAS2R16 Protein and Its Single Nucleotide Variants in Pituitary Adenoma Development.

Pituitary adenoma (PA) is a common benign tumor that develops in the pituitary gland, causing hormonal imbalances and potential health issues. The TAS2R16 gene codes for a taste receptor and is involved in bitter taste perception, but there is currently no known direct link between this gene and pituitary adenoma. This study included 221 healthy controls and 131 patients with pituitary adenoma (PA) from the Lithuanian population. DNA was isolated from peripheral venous blood using the salt precipitation method. Genotyping was performed via RT-PCR. Statistical analysis was conducted with IBM SPSS Statistics 29.0 software, incorporating the Bonferroni correction for multiple comparisons. This study found that the TAS2R16 rs978739 C allele is less common in the non-invasive PA group compared to the control group (p = 0.045). The TAS2R16 rs860170 CT genotype reduces the likelihood of developing non-invasive PA by 1.9-fold under the codominant (p = 0.024) and overdominant (p = 0.030) models. The odds of developing non-invasive PA are reduced by 2-fold under the dominant (p = 0.021) model for TAS2R16 rs860170 CT + CC genotypes and by 2-fold under the additive (p = 0.018) model for each TAS2R16 rs860170 C allele. The PA group had higher serum levels of TAS2R16 than the control group (p < 0.001). The present study found that patients with the TAS2R16 rs978739 TT or CT genotype had higher serum TAS2R16 levels and protein concentrations than healthy individuals (p = 0.025 and p = 0.019, respectively), and those with the AA or AG genotype of TAS2R16 rs1357949 had higher protein concentrations (p = 0.005 and p = 0.007, respectively). The TAS2R16 rs978739 C allele was less common in the non-invasive PA group compared to the control group, while the TAS2R16 rs860170 CT genotype was linked to a reduced likelihood of developing non-invasive PA. Additionally, the PA group showed higher serum levels of TAS2R16, and increased serum protein concentrations were observed in PA patients with specific TAS2R16 variants.

Population Genomic Scans for Natural Selection and Demography.

Uncovering the fundamental processes that shape genomic variation in natural populations is a primary objective of population genetics. These processes include demographic effects such as past changes in effective population size or gene flow between structured populations. Furthermore, genomic variation is affected by selection on nonneutral genetic variants, for example, through the adaptation of beneficial alleles or balancing selection that maintains genetic variation. In this article, we discuss the characterization of these processes using population genetic models, and we review methods developed on the basis of these models to unravel the underlying processes from modern population genomic data sets. We briefly discuss the conditions in which these approaches can be used to infer demography or identify specific nonneutral genetic variants and cases in which caution is warranted. Moreover, we summarize the challenges of jointly inferring demography and selective processes that affect neutral variation genome-wide.

Renin and CYP P450 gene variations significantly associated with essential hypertension: A prospective pharmacogenomics study

ObjectiveThis study aims to investigate the association between Renin-angiotensin aldosterone system (RAAS) and Cytochrome P450 gene polymorphisms in hypertension patients of the South Indian population using pharmacogenomics profile. MethodsHypertension cases (N = 147) and control subjects (n = 150) were collected from Tamil Nadu, India. A case-control association study was conducted to assess the involvement of RAAS gene polymorphisms (REN rs397514691, REN rs544315427, REN rs567667202) and CYP gene polymorphisms (CYP2D6 rs754164689, CYP2D6 rs1058172, CYP3A4 rs765598920) in essential hypertensive patients. Genotyping was performed using the PCR-RFLP method, and significant results were validated through RT-PCR analysis. ResultsThe genotype and allele distribution of REN rs397514691 and rs544315427 variants significantly associated with hypertensive patients (Variant Allele Frequency (VAF) = 0.11; VAF = 0.27, respectively). CYP2D6 polymorphisms rs754164689 and rs1058172 variant alleles were significantly associated with female hypertensive patients, suggesting a potential risk allele for essential hypertension in the South Indian population. REN and CYP3A4 variants, highly connected in pharmacology action, were validated through RT-PCR amplification studies, providing new insights into their role in the development of hypertension. Association confirmation was achieved through multifactor dimensionality reduction analysis. ConclusionThe genes associated with specific variants, particularly REN and CYP2D6, may serve as potential markers for the early diagnosis of hypertension and as new drug targets, particularly in the female population.

Whole-exome sequencing uncovers the genetic complexity of bicuspid aortic valve in families with early-onset complications

Bicuspid aortic valve (BAV) is the most common congenital heart lesion with an estimated population prevalence of 1%. We hypothesize that specific gene variants predispose to early-onset complications of BAV (EBAV). We analyzed whole-exome sequences (WESs) to identify rare coding variants that contribute to BAV disease in 215 EBAV-affected families. Predicted damaging variants in candidate genes with moderate or strong supportive evidence to cause developmental cardiac phenotypes were present in 107 EBAV-affected families (50% of total), including genes that cause BAV (9%) or heritable thoracic aortic disease (HTAD, 19%). After appropriate filtration, we also identified 129 variants in 54 candidate genes that are associated with autosomal-dominant congenital heart phenotypes, including recurrent deleterious variation of FBN2, MYH6, channelopathy genes, and type 1 and 5 collagen genes. These findings confirm our hypothesis that unique rare genetic variants drive early-onset presentations of BAV disease.

MECP2 Variants in Males: More Common Than Previously Appreciated

ObjectiveTo assess the age and MECP2 variants of recently identified males and set the stage for further study of clinical features in males. MethodsGenetic information on the specific MECP2 variant was acquired from the coordinator (KF) of the Parent Group for Males. Data were collected indicating whether these variants were de novo or transmitted from the mother and whether males who appeared to meet the diagnostic criteria for Rett syndrome (RTT) had mosaicism for the MECP2 variant. ResultsFifty-nine males were identified through the parent group. Their ages ranged from 2 to 28 years, with the median age being 7.0 years and the mean age being 10.8 years. Of these variants, forty-six (78.0%) were de novo, nine (15.3%) were maternally inherited, and for four (6.8%), inheritance was not known. Eleven (18.6%) were mosaic, 10 with somatic mosaicism and one with Klinefelter syndrome (47XXY). Together with males reported previously from the US Natural History Study, the total group represents 85 males, of whom 27 are deceased. ConclusionThese data on males with MECP2 variants are important to caregivers, physicians, and researchers to begin to characterize their historical and clinical features, to improve diagnostic recognition and overall care, and to accelerate access to therapeutic studies including gene replacement strategies. Equal access to such therapies for males is critical.

PiRNA PROPER Suppresses DUSP1 Translation by Targeting N6-Methyladenosine-Mediated RNA Circularization to Promote Oncogenesis of Prostate Cancer.

Genetic and epigenetic alterations occur in many physiological and pathological processes. The existing knowledge regarding the association of PIWI-interacting RNAs (piRNAs) and their genetic variants on risk and progression of prostate cancer (PCa) is limited. In this study, three genome-wide association study datasets are combined, including 85,707 PCa cases and 166,247 controls, to uncover genetic variants in piRNAs. Functional investigations involved manipulating piRNA expression in cellular and mouse models to study its oncogenetic role in PCa. A specific genetic variant, rs17201241 is identified, associated with increased expression of PROPER (piRNA overexpressed in prostate cancer) in tumors and are located within the gene, conferring an increased risk and malignant progression of PCa. Mechanistically, PROPER coupled with YTHDF2 to recognize N6-methyladenosine (m6A) and facilitated RNA-binding protein interactions between EIF2S3 at 5'-untranslated region (UTR) and YTHDF2/YBX3 at 3'-UTR to promote DUSP1 circularization. This m6A-dependent mRNA-looping pattern enhanced DUSP1 degradation and inhibited DUSP1 translation, ultimately reducing DUSP1 expression and promoting PCa metastasis via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Inhibition of PROPER expression using antagoPROPER effectively suppressed xenograft growth, suggesting its potential as a therapeutic target. Thus, targeting piRNA PROPER-mediated genetic and epigenetic fine control is a promising strategy for the concurrent prevention and treatment of PCa.

Patterns of pharmacogenetic variation in nine biogeographic groups.

Frequencies of pharmacogenetic (PGx) variants are known to differ substantially across populations but much of the available PGx literature focuses on one or a few population groups, often defined in nonstandardized ways, or on a specific gene or variant. Guidelines produced by the Clinical Pharmacogenetic Implementation Consortium (CPIC) provide consistent methods of literature extraction, curation, and reporting, including comprehensive curation of allele frequency data across nine defined "biogeographic groups" from the PGx literature. We extracted data from 23 CPIC guidelines encompassing 19 genes to compare the sizes of the populations from each group and allele frequencies of altered function alleles across groups. The European group was the largest in the curated literature for 16 of the 19 genes, while the American and Oceanian groups were the smallest. Nearly 200 alleles were detected in nonreference groups that were not reported in the largest (reference) group. The genes CYP2B6 and CYP2C9 were more likely to have higher frequencies of altered function alleles in nonreference groups compared to the reference group, while the genes CYP4F2, DPYD, SLCO1B1, and UGT1A1 were less likely to have higher frequencies in nonreference groups. PGx allele frequencies and function differ substantially across nine biogeographic groups, all but two of which are underrepresented in available PGx data. Awareness of these differences and increased efforts to characterize the breadth of global PGx variation are needed to ensure that implementation of PGx-guided drug selection does not further widen existing health disparities among populations currently underrepresented in PGx data.

Colocalised Genetic Associations Reveal Alternative Splicing Variants as Candidate Causal Links for Breast Cancer Risk in 10 Loci.

Genome-wide association studies (GWASs) have revealed numerous loci associated with breast cancer risk, yet the precise causal variants, their impact on molecular mechanisms, and the affected genes often remain elusive. We hypothesised that specific variants exert their influence by affecting cis-regulatory alternative splice elements. An analysis of splicing quantitative trait loci (sQTL) in healthy breast tissue from female individuals identified multiple variants linked to alterations in splicing ratios. Through colocalisation analysis, we pinpointed 43 variants within twelve genes that serve as candidate causal links between sQTL and GWAS findings. In silico splice analysis highlighted a potential mechanism for three genes-FDPS, SGCE, and MRPL11-where variants in proximity to or on the splice site modulate usage, resulting in alternative splice transcripts. Further in vitro/vivo studies are imperative to fully understand how these identified changes contribute to breast oncogenesis. Moreover, investigating their potential as biomarkers for breast cancer risk could enhance screening strategies and early detection methods for breast cancer.

Role of ACE2 and TMPRSS2 polymorphisms in clinical severity and outcomes of COVID-19 in Egypt.

The clinical presentations of coronavirus disease 2019 (COVID-19) exhibit significant variation, ranging from asymptomatic cases to mortality resulting from severe pneumonia. Host genetics can partially explain this variation. This study evaluated possible associations between severity and outcome of COVID-19 and single nucleotide polymorphism (SNP) rs2285666 in the ACE2 gene and SNP rs2070788 in the TMPRSS2 gene. The study included a sample of 100 consecutive adult patients admitted to the COVID-19 Isolation and Intensive Care Units of the Zagazig University Hospitals, Zagazig, Egypt from July 2021 to November 2021. For rs2285666, polymerase chain reaction-restriction fragment length polymorphism was carried out. For rs2070788, real-time polymerase chain reaction was performed. For rs2285666, the GA genotype was the most frequent among female patients (39% [16/41]) and the A genotype was more prevalent among male patients (54.2% [32/59]). For rs2070788, the AA genotype was the most frequent among all patients (46% [46/100]). No rs2285666 or rs2070788 genotypes or allele frequencies had significant associations with either severity or outcomes of patients. This study found no significant associations of COVID-19 severity or outcomes of patients with genotypes or allele frequencies of the rs2285666 SNP in the ACE2 gene or the rs2070788 SNP of the TMPRSS2 gene. The search for other genetic associations with COVID-19 infection is still required. The study reveals that host genetics explain the variation observed in the disease. Specific genetic variants can confer either increased susceptibility or resistance to the disease.

Generalized fixed drug eruption suggesting potential association with dimenhydrinate: A rare case report

Generalized fixed drug eruption (GFDE) is a specific variant of fixed drug eruption (FDE) characterized by multifocal lesions that recur upon exposure to a particular medication. This report describes a rare case of GFDE in a 54-year-old male, who presented with chief complaints of widespread erythema and pruritic, burning sensation. Physical examination revealed the patient to be in generally good condition dermatological status showed erosion on the hard palate, patches, erythematous macules, and partially ruptured bullae forming erosion in inguinal and genitals area, buttocks, thighs, lower legs, feet, axillae, hands, forearms, and back. The lesions were described as purplish round/oval erythematous patches, ranging from 1-4 cm in diameter, partially confluent, forming larger areas up to 6x7 cm, with bullae partially ruptured into erosion. The patient was admitted to the hospital, and treated with Ringer's lactate infusion, and an intravenous injection of 125 mg methylprednisolone. On the second day, the dose of intravenous methylprednisolone was reduced to 62.5 mg in the morning and the patient was administered a 10 mg cetirizine tablet orally in the evening, triamcinolone acetonide for oral lesions, a 15-minute NaCl 0.9% compress on the genitals twice a day, and desoximetasone 0.25% cream for all lesions. By the third day, the patient’s condition had improved, and he was then discharged. The prescribed home therapy regimen included a 16 mg methylprednisolone tablet in the morning, a 4 mg tablet in the afternoon, a 10 mg cetirizine tablet once daily, a 500 mg ciprofloxacin tablet twice daily, compress, and topical applications of triamcinolone acetonide for oral lesions and desoximetasone 0.25 % cream for all other lesions. A follow-up visit three days post-discharge indicated significant dermatological improvement. The diagnosis was established through anamnesis, physical examination, and appearance of skin disorder. Dimenhydrinate was identified as the potential causative agent.

Digital HRM with Machine Learning Approach

The purpose of this paper is to provide an overview of how modern resource management resolves conventional challenges in that area. Computing technology with all its specific application variants will help human performance in HR management in the contemporary era. The rapid advancement of technology and digitalization has presented a digital economy characterized by business and the trade transactions based on technology. This study aims to analyze the influence of the digital economy as measured by the Value of Electronic Money Transactions and the Value of E-Commerce Transactions on Indonesia’s economic growth. This research method is descriptive qualitative with a literature study approach. The data sources used are journal manuscripts, books, and other sources that are in accordance with the theme of this study. The data will be elaborated to get the construction of relevant thoughts and reflect an adequate analysis of computers and human resource management in this modern era. The results of the study are computing is able to carry out administrative tasks automatically; computing is able to increase employee engagement; computing can help improve the recruitment and orientation process; computing can help ensure compliance; and computing can help drive data-driven decision making.

Influence of Single Nucleotide Polymorphisms on CRS Outcomes: A Preliminary Observational Study.

To conduct a preliminary investigation into the relationship between specific SNP variants, type II inflammation, and the effectiveness of dupilumab therapy and surgery in patients with CRS. In this prospective study, 48 subjects were enrolled, comprising 32 CRS patients and 16 healthy controls. The CRS patients were subjected to either dupilumab therapy or endoscopic surgery according to EPOS guidelines. SNP variants were identified using the TaqMan SNP genotyping technique. The identified SNP profiles were compared between the control group and CRS patients, and their potential influence on treatment outcomes was evaluated. Treatment responses were assessed based on symptom scores, such as SS-I, SNOT-22, disease progression using the NPS findings, and SNP profiles at a 6-month follow-up. The primary measures included the Nasal Polyp Score, Smell Identification Test (SIT) score, and SNOT-22 outcomes. Dupilumab therapy and surgery significantly decreased NPS, with the last showing superior results. However, dupilumab therapy resulted in a significantly improved SIT score. Significant differences were observed in SNP profiles, particularly with rs1800629 (TNFA), rs2856838 (IL1a), rs17561 (IL1a), and rs1805011 (IL4R). In particular, the expression of rs2856838 and rs1805011 variants in the dupilumab group was associated with significantly better SIT and SNOT-22 outcomes than non-expressors. Also, the surgery group patients expressing the rs2856838 variant reported significant improvements in SNOT-22 scores. These preliminary findings suggest that SNP genotypes may guide personalized treatment strategies for CRS. Further larger prospective studies are required to confirm these initial observations. 2 Laryngoscope, 2024.

Exploration of Developmental Variants of Predatory Ladybird, Coccinella septumpunctata L. (Coleoptera: Coccinellidae) on an Artificial Diet.

This study aimed to focus on the identification, rearing, and exploration of developmental variants of the predatory ladybird, Coccinella septempunctata L., renowned for its efficacy as a biological control agent and its predation on agricultural pests. However, comprehensive knowledge concerning the occurrence and characteristics of developmental variants in this species remains limited. In this study, through meticulous monitoring and exploration, we identified developmental variants exhibiting distinct sexual attributes, as well as survival rates. The research outcomes enhance our understanding of the developmental variations within an egg batch of C. septempunctata. Moreover, the findings hold practical implications for the implementation of biological control strategies in agriculture, as specific variants may possess unique characteristics that enhance their effectiveness as natural enemies against pests.

Assessment the carrier frequency of monogenic diseases in populations requiring assisted reproductive technology

PurposeThe objective of this study is to assess the carrier frequency and pathogenic variation of monogenetic diseases in a population of 114 subjects in Han Chinese from Hebei province who are undergoing assisted reproductive technology through the utilization of Expanded Carrier Screening (ECS).MethodsThe study utilized a panel consisting of 155 severe monogenic recessive genetic diseases for ECS. Next-generation sequencing technology was employed to identify specific variants associated with ECS in a cohort of 114 subjects from 97 couples, comprising 97 females and 17 male spouses.ResultsA total of 114 individuals received ECS. The carrier rate of pathogenic genes in the enrolled population was 44.74% (51/114). Among the 97 females, the carrier rate of pathogenic genes was higher in those without assisted reproduction indicators than in those with assisted reproduction indicators (59.09% vs. 41.33%). However, the carrier rate of pathogenic genes in males without assisted reproductive technology was slightly lower than that with assisted reproductive technology (40% vs. 41.67%). Among both female and male participants, the carrier rate of pathogenic genes between individuals without indicators of assisted reproduction and those with such indicators was 55.55% vs. 41.38%. In 51 carriers, 72.55% (37/51) carried one genetic variant, 25.49% (13/51) carried two genetic variants, and 1.96% (1/51) carried three genetic variants. A total of 38 pathogenic genes were detected in this study, and GJB2 and MMACHC were most common. The carrier rates of the two genes were both 5.26% (6/114). A total of 55 variations were detected, and c.235delC was most frequently found. The carrier rate was 3.51% (4/114). The incidence of couples carrying the same pathogenic genes was 1.03% (1/97).ConclusionsThe findings elucidate the carrier rate of pathogenic genes among 155 severe monogenic recessive genetic diseases and underscore the significance of ECS as a preventive measure against congenital anomalies. When both partners carry the same genetic mutation for a monogenic disease, preventive strategies can be taken in offspring through preimplantation genetic testing (PGT), prenatal genetic testing, or the utilization of donor gametes. ECS is instrumental in assessing reproductive risk, guiding fertility-related decisions, and reducing the prevalence of monogenic recessive genetic disorders in subsequent generations.