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Cardiovascular diseases (CVDs) are responsible for approximately 17.9 million deaths every year. There is growing evidence that circular RNAs (circRNAs) may play a significant role in the early diagnosis and treatment of cardiovascular diseases. As regulatory molecules, circular RNAs regulate gene expression, interact with proteins and miRNAs, and are translated into proteins that play a key role in a wide variety of biological processes, including the division and proliferation of cells, as well as the growth and development of individuals. An overview of the properties, expression profiles, classification, and functions of circRNAs is presented here, along with an explanation of their implications in cardiovascular diseases including heart failure, hypertension, ischemia/reperfusion injury, myocardial infarction, cardiomyopathies, atherosclerosis, and arrhythmia.
Assuntos
Doenças Cardiovasculares , MicroRNAs , Humanos , RNA Circular/genética , Doenças Cardiovasculares/metabolismo , MicroRNAs/genética , Proteínas , Diagnóstico Precoce , RNA/metabolismoRESUMO
Schizophrenia spectrum disorders (SSD) are a group of diseases characterized by one or more abnormal features in perception, thought processing and behavior. Patients suffering from SSD are at risk of developing life-threatening complications. Pharmacogenetic studies have shown promising results on personalized treatment of psychosis. In the current study, 103 patients diagnosed with SSD treated with risperidone as antipsychotic monotherapy were enrolled. Socio-demographics and clinical data were recorded, and laboratory tests and genotyping standard procedure for cytochrome P450 (CYP) 2D6*4 were performed. Patients were evaluated by the Positive and Negative Syndrome Scale (PANSS) on admission and at discharge. Based on the reduction in the PANSS total score, subjects were divided into non-responders, partial responders and full responders. Only 11 subjects had a full response to risperidone (10.67%), 53 subjects (51.45%) had a partial response, and 39 participants (37.86%) were non-responders. Patients at first episode psychosis showed significantly higher levels of blood glucose and prolactin levels, while chronic patients showed significantly higher LDL levels. Adverse drug reactions (ADR) such as tremor and stiffness significantly correlated with genetic phenotypes (p = 0.0145). While CYP2D6 showed no impact on treatment response, ADR were significantly more frequent among poor and intermediate metabolizers.
Assuntos
Antipsicóticos , Citocromo P-450 CYP2D6 , Risperidona , Esquizofrenia , Humanos , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Risperidona/efeitos adversos , Risperidona/uso terapêutico , Masculino , Feminino , Esquizofrenia/tratamento farmacológico , Adulto , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Pessoa de Meia-Idade , Genótipo , Adulto JovemRESUMO
Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of <35% was observed in 41.9% of patients with disease-causing variants and 55% with negative or uncertain findings. Further genotype-phenotype correlations were explored in this study population. The substantial percentage (50.8%) of disease-causing variants identified in patients with DCM acknowledges the importance of genetic investigations. This study highlights the genetic landscape in genes associated with DCM in the Romanian population.
Assuntos
Cardiomiopatia Dilatada , Adulto , Humanos , Pessoa de Meia-Idade , Romênia , Volume Sistólico , Função Ventricular Esquerda , Etnicidade , Morte Súbita CardíacaRESUMO
Background: Preeclampsia (PE) is a critical condition affecting pregnancies worldwide. Understanding its etiology, particularly the genetic factors, is vital. This study aims to investigate the association between ACE gene polymorphisms, specifically the ACE G2350A (rs4343) variant, and the predisposition to PE, offering insights into the genetic predisposition towards this complex condition. Methods: A case-control study was conducted with 140 participants without PE (Control Group) and 128 participants diagnosed with PE (PE Group). The study focused on comparing the prevalence of the rs4343 polymorphism between the groups. Results: The analysis identified a significantly reduced risk associated with the AG genotype and an insignificant increase in risk with the AA genotype. Statistically significant differences in demographic and clinical characteristics, such as BMI and marital status, were observed between the groups, suggesting a multifaceted risk profile for PE that includes genetic, environmental, and socio-economic factors. Conclusions: The study highlight the significant role of genetic variations, specifically the ACE G2350A (rs4343) polymorphism, in influencing PE predisposition. It highlights the intricate interplay between genetic predispositions and other risk factors in the development of PE. Further research is encouraged to expand on these findings and explore a wider range of genetic polymorphisms and their interactions with environmental factors.
Assuntos
Predisposição Genética para Doença , Pré-Eclâmpsia , Humanos , Pré-Eclâmpsia/genética , Pré-Eclâmpsia/epidemiologia , Feminino , Gravidez , Estudos de Casos e Controles , Adulto , Fatores de Risco , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Fatores Socioeconômicos , Genótipo , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.
Assuntos
Síndrome Metabólica , Micronutrientes , Obesidade , Humanos , Masculino , Projetos Piloto , Método Duplo-Cego , Feminino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/dietoterapia , Adulto , Micronutrientes/uso terapêutico , Micronutrientes/administração & dosagem , Síndrome Metabólica/complicações , Síndrome Metabólica/dietoterapia , Fígado Gorduroso/complicações , Fígado Gorduroso/dietoterapia , Suplementos NutricionaisRESUMO
Background and Objectives: Psoriasis is a chronic and inflammatory condition that has a huge impact on the patient's quality of life. Biological treatment improved psoriasis therapy, with impressive results seen in the evolution of the disease and the patient's quality of life. However, the risk of mycobacterium tuberculosis (MTB) infection reactivation is well-known to biological therapy, which raises problems especially in an endemic country. Materials and Methods: In this study, we followed moderate to severe psoriasis patients who had latent tuberculosis infection (LTBI) following treatment with a biological therapy approved in Romania. Results: The patients were evaluated at baseline and then followed-up with Mantoux tests and chest X-rays every year, resulting in 54 patients being diagnosed with LTBI. At the initial evaluation, 30 patients with LTBI were identified, and 24 more were identified during biological therapy. These patients were given prophylactic treatment. Out of the 97 participants in this retrospective study, 25 required association of methotrexate (MTX) alongside biological therapy. We compared the prevalence of positive Mantoux tests in patients with combined therapy with that of patients only on biological treatment, and the results were higher in the combined therapy group. Conclusion: All the patients in the study were vaccinated against tuberculosis (TB) after birth, and none were diagnosed with active tuberculosis (aTB) before or after the start of therapy according to the pulmonologist.
Assuntos
Tuberculose Latente , Psoríase , Tuberculose , Humanos , Tuberculose Latente/epidemiologia , Tuberculose Latente/diagnóstico , Tuberculose Latente/microbiologia , Estudos Retrospectivos , Qualidade de Vida , Romênia/epidemiologia , Tuberculose/epidemiologia , Terapia Biológica , Psoríase/complicações , Psoríase/tratamento farmacológico , Psoríase/epidemiologiaRESUMO
Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients' health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.
Assuntos
Proteína BRCA1/genética , Distúrbios no Reparo do DNA/diagnóstico , Distúrbios no Reparo do DNA/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Fenótipo , Alelos , Biomarcadores , Estudos de Associação Genética/métodos , Humanos , Masculino , Linhagem , Avaliação de SintomasRESUMO
Few high-performance liquid chromatographyâ»tandem mass spectrometry (LC-MS/MS) methods have been developed for the full quantitation of fatty acids from human plasma without derivatization. Therefore, we propose a method that requires fewer sample preparation steps, which can be used for the quantitation of several polyunsaturated fatty acids in human plasma. The method offers rapid, accurate, sensitive, and simultaneous quantification of omega 3 (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and omega 6 fatty acids (arachidonic and linoleic acids) using high-performance LC-MS/MS. The selected fatty acids were analysed in lipid extracts from both free and total forms. Chromatographic separation was achieved using a reversed phase C18 column with isocratic flow using ammonium acetate for improving negative electrospray ionization (ESI) response. Mass detection was performed in multiple reaction monitoring (MRM) mode, and deuterated internal standards were used for each target compound. The limits of quantification were situated in the low nanomolar range, excepting linoleic acid, for which the limit was in the high nanomolar range. The method was validated according to the U.S. Department of Health and Human Services guidelines, and offers a fast, sensitive, and reliable quantification of selected omega 3 and 6 fatty acids in human plasma.
Assuntos
Bioensaio/métodos , Ácidos Graxos Ômega-3/sangue , Ácidos Graxos Ômega-6/sangue , Cromatografia Líquida de Alta Pressão/métodos , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Humanos , Limite de Detecção , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodosRESUMO
Worldwide, oral cancers represent the 6th most common type of cancer. Oral squamous cell carcinoma (OSCC), which is the most common type of oral cancer, is present in about 90% of the patients with this malignancy. OSCC presents a survival rate up to 80%, if it is detected in an early stage (T1), but if detected at later stages (T3 - T4) the survival rate decreases to 20 - 30%. Due to these survival rates, it is obvious that there is an urgent need to introduce new molecular biomarkers for the early, noninvasive diagnosis of oral cancers from saliva. These biomarkers will aid in increasing the survival rate of the patients for the long-term. MicroRNAs are part of a class of small, non-coding RNAs that contain 19 - 23 nucleotides. MicroRNAs play an important role in the regulation of biochemical mechanisms, cell proliferation, and other cellular mechanisms in the human body. Recently, due to the developments in the field of molecular genetics, salivary microRNAs became important biomarkers in early detection and monitoring of oral cancers by noninvasive methods. We want to present in this review the most important genetic and epigenetic biomarkers involved in oral carcinogenesis, focusing especially on the salivary microRNAs as biomarkers in early diagnosis of OSCC.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/genética , Epigênese Genética , MicroRNAs/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Carcinogênese , Inibidor p16 de Quinase Dependente de Ciclina , Ciclinas/metabolismo , Genômica , Humanos , Metaloproteinases da Matriz/metabolismo , Proteínas de Neoplasias/genética , Receptor ErbB-2/genética , Proteína do Retinoblastoma/genética , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
Cytochrome P450 1A2 (CYP1A2) is known to be the main enzyme directly responsible for caffeine metabolism. Rs762551 (NC_000015.10:g.74749576C>A) is a single nucleotide polymorphism of the CYP1A2 gene, and it is known mainly for metabolizing caffeine. A significant worldwide health issue, type 2 diabetes (T2DM), has been reported to be negatively associated with coffee consumption. Yet, some studies have proven that high intakes of coffee can lead to a late onset of T2DM. OBJECTIVES: This study aims to find any significant correlations among CYP1A2 polymorphism, coffee consumption, and T2DM. METHODS: A total of 358 people were enrolled in this study-218 diagnosed with T2DM, and 140 representing the control sample. The qPCR technique was performed, analyzing rs762551 (assay C_8881221) on the LightCycler 480 (Roche, Basel, Switzerland) with Gene Scanning software version 1.5.1 (Roche). RESULTS: Our first observation was that the diabetic patients were likely to consume more coffee than the non-diabetic subjects. People with the AA genotype, or the fast metabolizers, are the least common, yet they are the highest coffee consumers and present the highest glucose and cholesterol levels. Another important finding is the correlation between coffee intake and glucose level, which showed statistically significant differences between the diabetic group (p = 0.0002) and the control group (p = 0.029). CONCLUSIONS: The main conclusion of this study is that according to genotype, caffeine levels, glucose, and cholesterol are interconnected and proportionally related, regardless of type 2 diabetes.
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This study represents our second investigation into NIPT, involving a more extensive patient cohort with a specific emphasis on the high-risk group. The high-risk group was subsequently divided into two further groups to compare confirmed cases versus unconfirmed via direct methods. The methodology encompassed the analysis of 1400 consecutive cases from a single genetic center in western Romania, where NIPT was used to assess the risk of specific fetal chromosomal abnormalities. All high-risk cases underwent validation through direct analysis of fetal cells obtained via invasive methods, including chorionic villus sampling and amniocentesis. The confirmation process utilized QF-PCR, karyotyping, and SNP-Array methods customized to each case. Results: A high risk of aneuploidy at NIPT was identified in 36 out of 1400 (2.57%) cases and confirmed in 28 cases. The study also detected an increased risk for copy number variations (CNVs) in 1% of cases, confirmed in two instances involving one large microdeletion and one large microduplication. Trisomy 21 was the exclusive anomaly where NIPT confirmed all cases with identified risk. High-risk NIPT results which were not validated by invasive methods, were classified as false positives; parents in these cases determined to continue the pregnancy. In conclusion, NIPT can serve as a screening method for all pregnancies; however, in high-risk cases, an invasive confirmation test is strongly recommended.
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Pharmacogenetic markers are current targets for the personalized treatment of psychosis. Limited data exist on COMT and NRG1 polymorphisms in relation to risperidone treatment. This study focuses on the impact of COMT rs4680 and NRG1 (rs35753505, rs3924999) polymorphisms on risperidone treatment in schizophrenia spectrum disorders (SSDs). This study included 103 subjects with SSD treated with risperidone monotherapy. COMT rs4680, NRG1 rs35753505, and rs3924999 were analyzed by RT-PCR. Participants were evaluated via the Positive and Negative Syndrome Scale (PANSS) after six weeks. Socio-demographic and clinical characteristics were collected. COMT rs4680 genotypes significantly differed in PANSS N scores at admission: AG>AA genotypes (p = 0.03). After six weeks of risperidone, PANSS G improvement was AA>GG (p = 0.05). The PANSS total score was as follows: AA>AG (p = 0.04), AA>GG (p = 0.02). NRG1 rs35753504 genotypes significantly differed across educational levels, with CC>CT (p = 0.02), and regarding the number of episodes, TT>CC, CT>CC (p = 0.01). The PANSS total score after six weeks of treatment showed a better improvement for TTAssuntos
Antipsicóticos
, Catecol O-Metiltransferase
, Neuregulina-1
, Polimorfismo de Nucleotídeo Único
, Risperidona
, Esquizofrenia
, Humanos
, Neuregulina-1/genética
, Catecol O-Metiltransferase/genética
, Risperidona/uso terapêutico
, Esquizofrenia/tratamento farmacológico
, Esquizofrenia/genética
, Masculino
, Feminino
, Adulto
, Antipsicóticos/uso terapêutico
, Pessoa de Meia-Idade
, Medicina de Precisão/métodos
, Genótipo
RESUMO
BACKGROUND: The plasma level of antipsychotics and their metabolites depends on the activity of the cytochrome P450 (CYP) system in the liver. This research aims to test the individual response variability to atypical antipsychotic drugs, depending on the activity of the CYP2D6 enzyme. METHODS: In a prospective, noninterventional study, we included 56 adolescents, 51.79% male, diagnosed with schizophrenia. The patients underwent DNA sampling for genotyping SNP by RT-PCR and CYP* allelic variants using Applied Bio-systems™ TaqMan® Assays Foster City, CA, USA). and clinical and paraclinical assessments. The effectiveness of the therapy was evaluated with the PANSS scores at baseline and 3, 6, and 12 months after the initiation of an atypical antipsychotic treatment. RESULTS: Based on the genotyping results, the patients were divided into slow metabolizers (Group 1), extensive metabolizers (Group 2), and intermediate metabolizers (Group 3). The PANSS score showed a significant decrease in Group 2, compared to Group 3 after 3 (p = 0.02), 6 (p = 0.0009), and 12 months (p < 0.0001). The patients in Group 1 showed high PANSS scores, and those in Group 2 had fewer adverse reactions than the other groups. CONCLUSIONS: Assessing the CYP2D6 polymorphism may be useful in clinical pediatric psychiatric practice towards improving clinical results and patients' quality of life.
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BACKGROUND: Preeclampsia (PE) and eclampsia (E) are severe pregnancy complications with significant maternal and neonatal health impacts. This study explores the association of the rs5707 polymorphism in the renin-angiotensin system (RAS) with PE/E and related neonatal outcomes. MATERIALS AND METHODS: We conducted a cross-sectional study involving 400 mother-newborn dyads at the "Pius Brinzeu" Emergency Clinical Hospital Timisoara. Participants were divided into a control group (254 normotensive women) and a PE/E group (146 women with PE/E). Genotyping for the rs5707 polymorphism was performed using real-time PCR, and statistical analyses assessed associations with maternal body mass index (BMI) and neonatal outcomes. RESULTS: The AA genotype of rs5707 was significantly associated with a reduced risk of PE/E and more favorable neonatal outcomes, including higher Apgar scores, greater birth weights, and longer gestational ages. Conversely, the AC genotype correlated with increased maternal BMI and adverse neonatal outcomes. Odds ratios highlighted the protective effect of the AA genotype against PE/E and the increased risk associated with the AC genotype. CONCLUSIONS: This study revealed the critical role of the rs5707 polymorphism in PE/E development and neonatal health. Genetic screening for rs5707 could enhance early identification and personalized intervention strategies, improving outcomes for both mothers and neonates. Further research is needed to validate these findings across diverse populations and to uncover the underlying mechanisms.
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Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in childhood and rare in adults, while acute myeloid leukemia (AML) is less common in children and more common in older adults. The aim of the study was to present our experience for the diagnostic of leukemia by using the classic and molecular cytogenetic methods. The study was conducted between 2009 and 2019 within the Classic and Molecular Genetic Laboratory of the Oncohematology Department from the Louis Turcanu Emergency Hospital for Children, Timisoara, Romania. The study group included 337 children and adults, evaluated between 2009 and 2019. By using the conventional and molecular cytogenetic technique, the cytogenetic anomalies found were 35 numerical chromosomal abnormalities, 10 (9;22)(q34;q11) [four ALL, one AML, five chronic myeloid leukemia (CML)] translocations, nine (15;17)(q24;q21) translocations, three (14;14)(q11;q32) translocations, two (4;11)(q21;q23) translocations, one (1;14)(p32;q11) translocation, one (7;14)(qter;q11) translocation, one (8;21)(q22;q22) translocation, one (9;14)(p12;q32) translocation, seven rearrangements of the MLL gene and two rearrangements of the core-binding factor subunit beta∕myosin heavy chain 11 (CBFB∕MYH11) gene. The use of conventional and molecular cytogenetic analysis is one of the most important prognostic indicators in acute leukemia patients, allowing the identification of biologically distinct subtypes of disease and selection of appropriate treatment approaches.
Assuntos
Leucemia , Humanos , Romênia , Feminino , Masculino , Adulto , Criança , Adolescente , Pré-Escolar , Leucemia/genética , Leucemia/patologia , Leucemia/diagnóstico , Análise Citogenética/métodos , Pessoa de Meia-Idade , Adulto Jovem , Idoso , Aberrações Cromossômicas , LactenteRESUMO
The existence of two sequential lymphomas, one localized and one systemic, either both with B or T lymphocytes, or one with B cells and one with T cells, with the same patient, is a known possibility. The second lymphoma is often induced by immunodepression or by the initial treatment. However, the existence of two cutaneous lymphomas with different cell lines, without systemic involvement, represents an uncommon situation. In this report, we describe the case of a 37-year-old man with an initial diagnosis of PMZBCL that over 10 months also developed a MF patch/plaque on the left leg.
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Cardiofaciocutaneous (CFC) syndrome [Online Mendelian Inheritance in Man (OMIM) #115150] is characterized by craniofacial dysmorphism, heart malformation, ectodermal abnormalities, neuromotor delay and intellectual disability. It is not a frequent disease, about 300 cases have been reported in the medical literature. We describe the case of a 34-year-old patient presenting with CFC syndrome phenotype, monitored since the age of 1 1∕2 years. Clinical findings included craniofacial dysmorphism, development delay, heart malformation and severe intellectual disability. The evolution was with progressive intellectual disability, hypogonadism, hypertrophic cardiomyopathy, wrinkled palms and soles. Molecular analysis showed a heterozygous variant in the B-Raf proto-oncogene, serine∕threonine kinase (BRAF) gene (7q34): NM_001354609.2:c.1502A>G, with pathogenic significance. We report this case, observed along a period of 33 years, for illustration of clinical evolutive particularities, and for difficulties in establishing the positive diagnosis.
Assuntos
Displasia Ectodérmica , Cardiopatias Congênitas , Deficiência Intelectual , Adulto , Displasia Ectodérmica/genética , Fácies , Insuficiência de Crescimento , Cardiopatias Congênitas/genética , Humanos , Deficiência Intelectual/genética , Estudos Longitudinais , Proteínas Proto-Oncogênicas B-rafRESUMO
The benefit of reporting unsolicited findings in Next Generation Sequencing (NGS) related to cancer genes in children may have implications for family members, nevertheless, could also cause distress. We aimed to retrospectively investigate germline variants in 94 genes implicated in oncogenesis, in patients referred to NGS testing for various rare genetic diseases and reevaluate the utility of reporting different classes of pathogenicity. We used in silico prediction software to classify variants and conducted manual review to examine unsolicited findings frequencies in 145 children with rare diseases, that underwent sequencing - using a 4813 gene panel. The anonymized reanalysis revealed 18250 variants, of which 126 were considered after filtering. Six pathogenic variants (in BRCA1,BMPR1A,FANCA,FANCC,NBN genes) with cancer related phenotype and three unsolicited variants (in BRCA2,PALB2,RAD50 genes) were reported to patients. Additionally, three unsolicited variants in ATR, BLM (in two individuals), and FANCB genes presented potential cancer susceptibility, were not reported to patients. In retrospect, 4.8% (7/145) of individuals in our cohort had unsolicited NGS findings related to cancer. More efforts are needed to create an updatable consensus in reporting variants in cancer predisposing genes, especially for children. Consent process is crucial to inform of both value and risk of additional genetic information.
Assuntos
Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Proteínas de Neoplasias/genética , Neoplasias/genética , Neoplasias/patologia , Criança , Feminino , Humanos , Masculino , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Oral cancer is a worldwide public health problem, being the sixth most common neoplasm. The high mortality rate of this type of cancer is due to a delayed diagnosis, a fast evolution and metastasis, no primary symptomatology, the multitude of risk factors and the lack of awareness among the population concerning oral malignancy. AIM: The aim of this 5-year retrospective study was to evaluate the incidence of oral cancer patients in the Clinic of Maxillo-Facial Surgery, Emergency County Hospital, Timisoara, Romania and quantify the histopathological (HP) subtypes, localization, age, gender, tumor staging and differentiation, positive loco-regional lymph nodes and risk factors. PATIENTS, MATERIALS AND METHODS: A number of 129 patients diagnosed with oral cancer were included in the study and their medical records were analyzed. A statistical analysis was performed that included the variables gender, age, tumor staging, differentiation grade, HP subtype, lymph nodes, localization, and risk factors. RESULTS: Our results outlined a high prevalence of oral cancer among males (65.9%), squamous cell carcinoma (SCC) being the most common HP subtype. Tumor staging revealed the fact that the majority of were T3 and T4 tumors with dissemination in the loco-regional lymph nodes. In 52% of the cases, tobacco was identified as a risk factor, and the association of tobacco and alcohol was present in 28.3% of the cases. CONCLUSIONS: The early diagnosis is crucial for the improvement of oral cancer survival rate. The oral cavity is permanently exposed to carcinogenic substances that associated with other risk factors have an influence upon the incidence of oral malignancies.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Humanos , Linfonodos/patologia , Metástase Linfática , Masculino , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/etiologia , Neoplasias Bucais/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de RiscoRESUMO
INTRODUCTION: Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention. PURPOSE: To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity. METHODS: One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software. RESULTS: Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model. CONCLUSION: The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.