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Abstract Background Ectodermal dysplasia syndactyly syndrome 1 (EDSS1) is a rare hereditary disorder characterized by defects in teeth, hair, and nails in association with a fusion of the digits. Genetically, the disease phenotypes are caused by homozygous and compound heterozygous variants in NECTIN4 gene. Objective The main objective of the study was to identify the pathogenic sequence variant(s) for family screening and identification of carriers. Methods In the present study, the authors have investigated a large consanguineous family of Pakistani origin segregating autosomal recessive EDSS1. All the coding exons of the NECTIN4 gene were directly sequenced using gene-specific primers. Results The affected individuals presented the classical EDSS1 clinical features including sparse hair, hypoplastic nails with thick flat discolored nail plates, peg-shaped, conical, and widely spaced teeth with enamel hypoplasia, proximal cutaneous syndactyly of fingers and toes. Sequence analysis of the coding region of the NECTIN4 identified a novel nonsense variant [c.163C>T; p.(Arg55*)] in exon-2 of the gene. Computational analysis of protein structure revealed that the variant induced premature termination at Arg55 located in Ig-like V-loop region leading to loss of Ig-C2 type domains and transmembrane region, and most likely Nectin-4 function will be lost. Study limitation Gene expression studies are absent that would have strengthened the findings of computational analysis. Conclusion The present study expanded the phenotypic and mutation spectrum of the NECTIN4 gene. Further, the study would assist in carrier testing and prenatal diagnosis of the affected families.
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Objective:To explore the prognostic value of poliovirus receptor(PVR) in patients with gastric cancer.Methods:Bioinformatics methods were used to analyze the expression of PVR mRNA in gastric cancer tissues and adjacent normal tissues and its relationship with prognosis. The clinicopathological data of 73 gastric cancer patients who underwent surgical treatment were retrospectively analyzed. Immunohistochemical method was used to detect the expression level of PVR in gastric cancer tissue and adjacent normal tissue, and its relationship with the clinicopathological characteristics of gastric cancer patients was analyzed.Results:The expression level of PVR mRNA in gastric cancer tissues was higher than that in adjacent normal tissues ( P<0.05). The expression of PVR is related to the clinical prognosis of gastric cancer patients, and the higher the expression of PVR, the lower the overall survival rate ( P=0.011) and the disease-free survival rate ( P=0.032) of gastric cancer patients. The results of immunohistochemical staining showed that PVR was highly expressed in gastric cancer tissue, mainly in the cytoplasm, while it was not expressed or lowly expressed in normal gastric tissue. High expression of PVR was associated with tumor size ( P=0.001) and recurrence 3-years after surgery ( P=0.013). Conclusions:PVR is overexpressed in gastric cancer tissue, and gastric cancer patients with high expression of PVR have a worse prognosis. The level of PVR has great value for the prognosis evaluation of gastric cancer patients.
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Context: Poliovirus (PV) receptor (CD155) is expressed on several kinds of cells and exerts diverse functions. Various investigations have confirmed that changes in CD155 expression in cancer cell lines affect metastasis, proliferation, and migration. Aims: The purpose of the present study was to investigate the CD155 transcript and protein expression in human colon adenocarcinoma cell lines in comparison to normal fetal human colon (FHC) cells. Materials and Methods: The CD155 expression level in four human adenocarcinoma cell lines and normal colon cell line were assessed using the SYBR green quantitative real-time polymerase chain reaction (PCR) and flowcytometry. Results: The results of real-time PCR indicated that CD155 was significantly overexpressed in all human adenocarcinoma cell lines (P = 0.000). The highest and the lowest expression level of CD155 messenger RNA was observed in SW480 and HT29 cell lines by 491.14, and 12.04 fold changes, respectively, in comparison with the human normal cell line (FHC). Results of flowcytometry indicate that protein was strongly expressed in cancer cell lines. SW480 cells showed the highest CD155 protein expression level of 98.1%, whereas this protein expression was 1.3% in human normal colon cell line (FHC). Totally, these data indicate that CD155 expression is significantly elevated in cancer cell lines. Conclusions: The preferential expression of CD155 on cancer cell lines rather than on normal cell line suggests that CD155 could be targeted for future PV virotherapy
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Background & objectives: It is important to understand the role of cell surface receptors in susceptibility to infectious diseases. CD155 a member of the immunoglobulin super family, serves as the poliovirus receptor (PVR). Heterozygous (Ala67Thr) polymorphism in CD155 has been suggested as a risk factor for paralytic outcome of poliovirus infection. The present study pertains to the development of a screening test to detect the single nucleotide (SNP) polymorphism in the CD155 gene. Methods: New primers were designed for PCR, sequencing and SNP analysis of Exon2 of CD155 gene. DNAs extracted from either whole blood (n=75) or cells from oral cavity (n=75) were used for standardization and validation of the SNP assay. DNA sequencing was used as the gold standard method. Results: A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150) of DNA samples tested by both SNP detection assay and sequencing. Interpretation & conclusions: The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.