Background Adams-Oliver syndrome (AOS [MIM 100300]) is a rare, multiple malformation syndrome commonly characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Brain abnormalities and heart defects are also present in most patients. Both autosomal-dominant and autosomal-recessive inheritance of the disease have been observed. To date, six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. Autosomal-recessive mutations are mostly associated with DOCK6 (MIM: 614219) and EOGT (MIM: 615297), while mutations in ARHGAP31 (MIM: 100300), RBPJ (MIM: 614814), NOTCH1 (MIM: 616028), and DLL4 (MIM: 616589) have been linked to autosomal-dominant inheritance. Case We report a case of AOS caused by DOCK6 mutations (c.3190_3191del and c.4491 + 1G > T), showing no signs of scalp ACC or TTLD, but with bilateral ventricular dilation and ophthalmic abnormalities. Results of wholeexome high-throughput sequencing were analyzed using a combination of pathogenicity prediction algorithms, query of variant databases, and review of the literature. Candidate gene variation sites were identified for pedigree verification. Conclusions The correlation between the genotype and phenotype of AOS has great variability, and the specific pathogenesis of AOS remains to be further studied.
Background: Breast cancer (BC) is one of the most common causes of cancer death globally, with a 0.5% increasing incidence per year. Natural killer cells (NK) have a crucial function in immune surveillance mechanisms, which recognize class I human leukocyte antigen (HLA) molecules, expressed on the target cells, through their membrane receptors, called killer cell immunoglobulin-like receptors (KIR). Impaired NK cell anti-tumor immunity has particular relevance with BC progression and metastases. KIRs are the most polymorphic receptors of NK cells that modulate NK cell activity against malignant cells through their interactions with their cognate HLA ligands. Materials and methods: Considering this issue, we conducted this study to survey the impact of HLA class I variegation on the susceptibility to the development of BC in Kermanshahi women. In our study, the presence of HLA-C1 and HLAC2 allotypes, HLA-B Bw4 and Bw6 dimorphism, as well as HLA-A Bw4 group, were detected using polymerase chain reaction with sequence-specific primers in 52 patients with breast cancer living in Kermanshah province (Iran) and 40 healthy subjects.Results: Here, we found that the presence of HLA-C1 allotype and HLAC1/HLAC2 genotype was significantly reduced in breast cancer patients compared to the healthy controls (P = 0.041, P = 0.005 respectively). No significant differences were found for HLA-C2, HLA-B Bw4 groups, HLA-B Bw6, and HLA-A Bw4, as well as their genotype.Conclusion: Our results indicated the protective role for HLA-C1allotype and HLAC1/HLAC2 genotype in healthy subjects compared to patients with breast cancer.
Background: Non-small cell lung cancer (NSCLC) is the principal subtype of lung cancer. Among all therapeutic options, platinum-based chemotherapy agents, especially Cisplatin, are still commonly used treatment for NSCLC patients. However, developing chemoresistance in NSCLC cells often gives rise to chemotherapy failure. Therefore, more studies are required to shed light on gene interaction and cellular pathways involved in initiating and developing resistance to platinum-based chemotherapy in NSCLC. Hence, it is urgent to find the key genes, microRNA (miRNAs), and potential molecular mechanisms implicated in chemoresistance and present markers to predict response to platinum-based chemotherapy in NSCLC patients. Methods: The microarray datasets GSE6410, GSE7035, GSE14814, GSE26704, GSE73302 were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using R software. Functional and pathway enrichment analyses were performed using the Enrich R site. Then, the protein-protein interaction (PPI) network and hub genes were obtained using the Cytoscape software. Further, the miRSystem database was performed to predict the miRNAs regulating the hub genes. Moreover, Cytoscape software and the CytoHubba plugin were used to construct the miRNA-target interaction network and hub modules. Finally, the Kaplan-Meier curve was used to demonstrate the survival curves and assess the association of the genes signature with clinical outcomes. Results: A total of 142 differentially expressed genes (DEGs) were found. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses present the p53 signaling pathway as the most significant pathway. Besides, from the top ten terms obtained of Biological Process, Molecular Function, and Cellular Component, the first ones, including cholesterol biosynthetic process, the extrinsic component of external side of plasma membrane, cytokine activity, were selected respectively. Based on the PPI network, the ten nodes with the highest degree were screened as hub genes. In addition, from the miRNA-target regulatory network in Cytoscape, ten hub nodes were found. Ultimately, according to Kaplan-Meier curve, BTG2 and TP53I3 with p-value <0.05 were associated with a better prognosis. Conclusions: In the present study, DEGs, candidate miRNAs, and underlying mechanisms involved in chemoresistance were identified to suggest potential biomarkers to provide new clues for the prediction of response to platinum-based chemotherapy.
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease that leads to axon demyelination and white matter plaque formation. The aim of the present study is to inspect the association between single nucleotide polymorphisms (SNPs) of IL4 (rs2070874), IL17A (rs2275913), and IL33 (rs7044343) and MS predisposition. The genotyping of the three genetic variants was conducted through tetra-plex-based real-time polymerase chain reaction (T-plex RT-PCR) method combined with the SYBR green fluorescent dye. Sixty-eight Iraqi MS patients and fifty healthy individuals (controls) were enrolled, and their DNA was extracted from whole blood. The optimum annealing/extension temperature was set at 58 degrees C. For each SNP, allele-specific fragments were identified by their melting points generated through real-time PCR. Agarose gel electrophoresis was performed to confirm the results. The distribution of the IL4 SNP genotypes in patients and controls was in good agreement with Hardy-Weinberg equilibrium, while there was a skewness from Hardy-Weinberg equilibrium in patients' group for both IL17A and IL33 SNPs. Multinomial logistic regression analysis was performed to investigate the association between the studied variants under four genetic models (dominant, recessive, over-dominant, and co-dominant) and MS risk. However, there were no significant differences in genotype/allele frequencies of three SNPs between patients and controls. Taken together, our study indicated that genotype/allele of IL4 (rs2070874), IL17A (rs2275913), and IL33 (rs7044343) SNPs may not play a considerable role in the predisposition to MS in this sample of the Iraqi population. However, SYBR green-dependent T-plex RT-PCR can be a cost-effective, reproducible and simple method for genotyping SNPs of interest.
Background: Proprotein convertase subtilisin/kexin type 9, a member of the serine protease family, plays an important role in the regulation of plasma low density lipoprotein cholesterol by stimulating the degradation of LDL receptor. Method: In this meta-analysis, we explored the correlation of PCSK9 polymorphisms E670G and D374Y with the elevated plasma lipid levels, which leads to a condition known as hypercholesterolemia, by calculating the standardized mean difference and Odds Ratio with 95% confidence interval. The statistical analysis was done using SPSS version. Results: Under dominant genetic model, pooled results had shown that PCSK9 E670G polymorphism was associated with higher LDL-C levels among the Asians (SMD = 0.53; I-2 = 40%; OR = 0.7610; 95% CI = 0.6554 to 0.8837 and p value = 0.003). Conclusion: The close relationship between both polymorphisms of PCSK9 gene i.e. E670G and D374Y, with the elevated plasma LDL-C levels has been observed. E670G polymorphism is highly prevalent among the Asian population.
