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BACKGROUND Innate immunity was found to be associated with both persistence of Helicobacter pylori (H. pylori) infection and increased risk of gastric cancer. AIM To identify the risk factors associated with H. pylori infection and to establish the role of TLR9 rs352140 in suppressing or promoting inflammation related to this infection in children. METHODS We performed a study of 155 children with digestive symptoms, who were divided into two groups according to the histopathological exam: Group 1 – 48 children with H. pylori-induced chronic gastritis, and Group 2 – control group. RESULTS Rural area and poor living conditions were significantly associated with H. pylori chronic gastritis (P = 0.0042/P < 0.0001). Both positive immunoglobulin A anti H. pylori and the rapid urease test were significantly associated with H. pylori infection (P < 0.0001). Significantly higher values of leukocytes and neutrophils within the peripheral blood were found in children with H. pylori chronic gastritis (P = 0.111/P = 0.284). We found a significant positive correlation between the variant TT genotype of TLR9 rs352140 polymorphism and both leucocytes and neutrophils (P = 0.0225/P = 0.0292). CONCLUSION Variant TT genotype carriers of the TLR9 rs352140 gene polymorphism might have a more severe degree of inflammation.

Background Cytokines were correlated with survival and disease progression in acute myeloid leukemia (AML). We aimed to evaluate the multivariate effect of TNF‐α rs361525, rs1800750, rs1800629, IL‐10 rs1800896, rs1800872, IL‐6 rs1800795, TGF‐β1 rs1800470, IFN‐γ rs2430561 single nucleotide polymorphisms (SNPs) on AML risk, the multivariate effect of SNPs on overall survival (OS) in AML and the association between the investigated SNPs and prognostic factors in AML. Methods All SNPs were genotyped in 226 adult AML cases and 406 healthy individuals. AML patients were investigated for FLT3 (ITD, D835), DNMT3A (R882), and NPM1 type A mutations. Results Univariate analysis revealed that age above 65 years had a negative influence on survival (P 2, lactate dehydrogenase (LDH) level, platelet (PLT) count, We aimed to evaluate the multivariate effect of TNF‐α rs361525, rs1800750, rs1800629, IL‐10 rs1800896, rs1800872, IL‐6 rs1800795, TGF‐β1 rs1800470, IFN‐γ rs2430561 single nucleotide polymorphisms (SNPs) on AML risk, the multivariate effect of SNPs on overall survival (OS) in AML and the association between the investigated SNPs and prognostic factors in AML. A negative association was observed between Eastern Cooperative Oncologic Group Scale status >2, lactate dehydrogenase (LDH) level, platelet (PLT) count

This study aimed to explore the associations between the TP53 rs1042522 (TP53 Arg72Pro), MDM2 rs2279744 (MDM2 309T&gt, G), rs3730485 (MDM2 del1518), MDM4 rs4245739 (MDM4 34091 C&gt, A) variants and odds of developing acute myeloid leukemia (AML) in a cohort of 809 adult subjects, consisting of 406 healthy controls and 403 AML patients. Model-based multifactor dimensionality reduction (MB-MDR) framework was used to identify the interactions of the mentioned variants and their association with AML risk. Associations of the mentioned variants with clinical features of AML, somatic mutations, and response to treatment were also evaluated. Significant associations between TP53 rs1042522 and MDM4 rs4245739 variants and AML susceptibility were noticed. MB-MDR and logistic regression analysis revealed an interaction between MDM2 rs2279744 and TP53 rs1042522, between MDM4 rs4245739 and MDM2 rs3730485, as well as significant associations with AML susceptibility. Several associations between the mentioned variants and clinical features of AML and somatic mutations were also noticed. Individually, the variant genotypes of TP53 rs1042522 and MDM4 rs4245739 were associated with AML susceptibility, but their interaction with MDM2 rs2279744 and rs3730485 modulated the risk for AML. The variant genotypes of TP53 rs1042522 were associated with adverse molecular and cytogenetic risk and also with NPM1 mutations.

Rationale: Co-occurrence of cytogenetic and molecular abnormalities is frequently seen in patients with acute myeloid leukemia (AML). The clinical outcome and genetic abnormalities of AML may vary; therefore, genetic investigation must be complex, using several techniques, to have an appropriate characterization of the AML genome and its clinical impact. The available molecular markers can predict prognosis only partially. Acute promyelocytic leukemia subtype M3 (AML M3) is a subtype of AML characterized by the presence of promyelocytic leukemia-retinoic acid receptor alpha (PML-RARA) genes fusion. Targeted treatment with all-trans-retinoic acid (ATRA) and ATRA combined with arsenic trioxide significantly improved the survival of AML M3 patients. Unknown prognostic factors could contribute to the early death of these patients. Patient Concerns: We present the case of a young female (20 years old) patient, who presented at the emergency department 5 months after giving birth to her first child, complaining of asthenia, fatigue, general musculoskeletal pain, and fever (38°C), symptoms having been present for the previous 6 days. The patient denied any chronic diseases in her medical and family history. Diagnosis: Laboratory analysis revealed severe pancytopenia. Cytogenetic and molecular analyzes revealed chromosomal abnormalities (trisomy 8), PML-RARA gene fusion, and fms-like tyrosine kinase 3 (FLT3) gene mutation. The immunophenotypic analysis was also suggestive for AML M3 according to the FAB classification. Interventions: Specific treatment was initiated for AML M3 and for secondary conditions. Molecular and cytogenetic analyzes were performed to have a more detailed characterization of the patient's genome. Outcome: Seventy-two hours after admission, she developed psychomotor agitation, confusion, coma, and convulsion. Subsequent deterioration and early death were caused by intracerebral hemorrhage with multiple localization and diffuse cerebral edema. Lessons: The presence of FLT3 internal tandem duplication (ITD) mutation may explain the rapid and progressive degradation of this AML M3 case and it may be used as a prognostic marker even when co-occuring with other markers such as PML-RARA gene fusion and trisomy 8. We consider that FLT3 ITD mutation analysis in young patients with AML should be performed as soon as possible. New strategies for patients’ education, AML (or cancers in general) prevention, and treatment are needed.

The main objective of the study was to evaluate the associations between MCM7 rs2070215, rs1527423, and rs1534309 single nucleotide polymorphisms (SNPs) and acute myeloid leukemia (AML) risk and prognosis. The secondary objectives were to assess if any relationships existed between the mentioned SNPs and FLT3, DNMT3A, NPM1 mutations with clinical outcomes and overall survival (OS) in AML patients. We investigated 281 AML cases and 405 healthy subjects. The results showed a significant association between a variant allele of rs2070215 (p = 0.007), CAT haplotype (p = 0.012), and AML susceptibility. No significant association was found between MCM7 variant genotypes and overall survival of AML patients (p &gt, 0.05), while several associations between somatic mutations, clinical and biological features, and poor OS were noticed. Lactate dehydrogenase (LDH) level &ge, 600 IU/L had a significant effect on the hazard of death (p = 0.004, HR = 1.49, 95% CI: 1.13&ndash, 1.95). Our study showed that the variant allele of rs2070215, in the allelic model, and CAT haplotype were associated with AML susceptibility. The investigated FLT3, DNMT3A, and NPM1 mutations were associated with the clinical and biological features and poor OS. LDH level &ge, 600 IU/L was associated with an increased hazard of death and this association remained significant when quantifying for effect modification by FLT3 mutation status.

Small supernumerary marker chromosome (sSMC) is a rare chromosomal abnormality and is detected in about 0.3% in cases with multiple congenital anomalies (MCA) and/or developmental delay. Different techniques for investigation of cases with MCA and/or developmental delay are available ranging from karyotyping to molecular cytogenetic technique and ultimately multiplex ligation dependent probe amplification (MLPA). Here we present a patient with multiple congenital anomalies for which classical cytogenetic technique was used as a first step in diagnosis and the results being confirmed by MLPA. The karyotype disclosed a sSMC considered to be a fragment of chromosome 22. The MLPA analysis using SALSA MLPA probemix P064-C2 Microdeletion Syndromes-1B confirmed the karyotype results, and according to the manufacturer’s recommendation we performed another confirmation analysis with MLPA probemix P311-B1 Congenital Heart Disease and MLPA probemix P250-B2 DiGeorge. We also suspected an Emanuel syndrome and performed another MLPA analysis with SALSA MLPA probemix P036-E3 Subtelomeres Mix 1 and probemix P070-B3 Subtelomeres Mix 2B for investigation of subtelomeric region that revealed a duplication of 11q25 region and the confirmation was performed using SALSA MLPA probemix P286-B2 Human Telomere-11. In conclusion, we consider that MLPA is a valuable method for identification of sSMC in children with developmental delay and congenital anomalies. Genetic diagnosis using different molecular techniques, such as MLPA, for increasing accuracy in identification of chromosomal structural aberrations has an important role in clinical diagnosis and in genetic counselling and our case explain the importance of using a specific laboratory technique for each stage of diagnosis.

Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR), providing information about the etiology of the genetic disorder. Muenke syndrome is produced by p.Pro250Arg mutation in FGFR3 gene with evidence of variable expressivity, representing 8% of the syndromic craniosynostoses. Here, we present the identification of a p.Pro250Arg pathogenic mutation (c.749C>G) in the FGFR3 gene using Multiplex Ligation-dependent Probes Amplification (MLPA) analysis in conjunction with Sanger sequencing in a patient with craniosynostosis and mild intellectual disability. The MLPA analysis detected a reduced signal of the probe, at the site of the c.749C>G mutation, defined by the presence of one allele of C749>G mutation in the FGFR3 gene, exon 7. Sanger sequencing was performed for confirmation and identified heterozygous p.Pro250Arg pathogenic variant (c.749C>G) in exon 7 of the FGFR3. In conclusion, we assessed the validity and clinical utility of the combined molecular genetic techniques, MLPA analysis, and Sanger sequencing, for craniosynostosis and intellectual disability, improving not only the diagnostic testing but also the genetic counseling and management of the disorder.

We assume that the CRISPR Cas9 theory must be delimited by applicability, because the consequences of long term DNA manipulation remain unknown. Moreover, the irreversibility of this procedure should instigate researchers to reserved opinions. Usefulness as well as benefits of CRISPR Cas9 made it one of the most popular and used genome editing technique. But with its huge potential, ethical and safety concerns emerge. Therefore, before continuing research in this direction we should have a well organized system that is able to make that differentiation between research and reproduction. However we truly believe in the future of genetic engineering and with the CRISPR-Cas9 system we expect that the opportunity of treating now so called incurable diseases arises. Time is all we need.

INTRODUCTION The oligophrenin-1 (OPHN1) gene, localized on the X chromosome, is a Rho-GTPase activating protein that is related to syndromic X-linked intellectual disability (XLID). XLID, characterized by brain anomalies, namely cerebellar hypoplasia, specific facial features, and intellectual disability, is produced by different mutations in the OPHN1 gene. PATIENT CONCERNS In this report, we present the clinical and molecular findings of a family affected by a mild XLID due to a deletion in the OPHN1 gene, exon 21, Xq12 region using Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The clinical features present in the family are a mild developmental delay, behavioral disturbances, facial dysmorphism, pes planus, nystagmus, strabismus, epilepsy, and occipital arachnoid cyst. INTERVENTIONS The MLPA analysis was performed for investigation of the copy number variations within the X chromosome for the family. DIAGNOSIS AND OUTCOME The MLPA analysis detected a deletion in the OPHN1 gene, exon 21 for the proband, and a heterozygous deletion for the probands mother. The deletion of the Xq12 region of maternal origin, including the exon 21 of the OPHN1 gene, confirmed for the probands nephew. LESSONS Our findings emphasize the utility of the MLPA analysis to identify deletions in the OPHN1 gene responsible for syndromic XLID. Therefore, we suggest that MLPA analysis should be performed as an alternative diagnostic test for all patients with a mild intellectual disability associated or not with behavioral disturbances, facial dysmorphism, and brain anomalies.

Background TLR4 is involved in H. pylori lipopolysaccharide recognition and its SNPs might be related to increased risk of developing premalignant conditions and gastric cancer. The objectives of the study were to evaluate the associations between both TLR4 rs4986790 and rs4986791 gene polymorphisms and H. pylori infection in children with gastritis. Methods We performed a cross-sectional study on 150 children admitted in a Tertiary Centre from Romania, between March 2016 and July 2018 in order to evaluate them regarding demographic, endoscopic, histopathological and TLR4 gene polymorphisms. Results Our final sample consisted of 50 children with H.pylori associated gastritis (group 1-Ghp group) and 97 children with gastritis without H.pylori infection (group 2). Poor socioeconomic status was a significant risk factor for H.pylori infection. We found no significant differences regarding the clinical symptoms and laboratory parameters between the two groups. Concordant results were found between the histopathological exam and rapid urease test. Variant genotypes of TLR4rs4986790 and TLR4rs4986791 gene polymorphisms acted as protective factors against H. pylori infection, without statistical significance. Conclusions The variant genotype of the TLR4 gene polymorphisms might be protective factors for H.pylori infection, while socioeconomic status is an risk factor for H. pylori infection. Urease test is a usefull diagnostic tool for H. pylori infection.

XRCC1 polymorphisms may alter the individual’s capacity to repair DNA damages and may increase the risk for developing different types of cancer, including Non-Hodgkin Lymphoma (NHL). The purpose of our study was to investigate the association between XRCC1 Arg194Trp and Arg399Gln polymorphisms and risk of NHL, in a case-control study consisted of 81 patients with NHL and 113 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods were performed to determine the XRCC1 genotypes. A statistically significant association was observed between the XRCC1 Arg194Trp polymorphism and risk of NHL (p0.0001, OR = 7.01, 95% CI = 2.488-19.753) in both male and female. We found no association between NHL and control groups with respect to XRCC1 Arg399Gln polymorphism (p = 0.4867, OR = 1.346, 95% CI = 0.5822-3.111). Also, we did not find differences between the XRCC1 polymorphisms and NHL risk taking into account the IPI score, ECOG performance status, Ann Arbor stage and the treatment outcome (p0.05, for all comparisons). Our results suggested an increased risk for NHL regarding the XRCC1 Arg194Trp polymorphism in a Romania population, while XRCC1 Arg399Gln polymorphism is not associated with NHL. Further work is needed to validate these results on a larger sample study.

IntroductionObjectiv. To investigate the contribution of TERT rs2736100 and rs2853669 gene polymorphisms in defining the genetic predisposition to AML, their association with different prognostic markers and their impact on survival, outcome and the prognosis of affected patients. Also, we investigated the association of TERT SNPs in AML in the presence or absence of DNMT3A (R882), NPM1 and FLT3 mutations.Material and methodsA total of 509 participants were enrolled in our study, consisting of 146 AML patients and 363 healthy participants, with no history of malignancy. TERT rs2736100 and rs2853669 polymorphisms were genotyped by using TaqMan SNP genotyping assays FLT3 (ITD, D835), DNMT3A (R882) and NPM1 c.863_864insTCTG (type A) mutation status was analyzed in each AML case.ResultsTERT rs2736100 and rs2853669 were not associated with AML risk in the codominant, dominant, recessive or allelic models. Multivariate Cox regression showed that TERT rs2853669 was a significant predictor for overall survival in AML patients. After adjusting for age, gender, cytogenetic risk group, ECOG status, FTLT3, DNM3A or NMP1 mutation, AML subtype and treatment, the estimated adjusted hasard ratio (HR adjusted=1.54, 95%CI:[1.01;2.35]) showed that the TERT rs2853669 variant genotype had a negative influence on survival time.ConclusionsTERT rs2853669 and rs2736100 polymorphisms were not risk factors for developing AML in the Romanian population, but TERT rs2853669 variant genotype had a negative effect on AML patients overall survival in the presence of other known prognostic factors.