RESUMO

BACKGROUND: In this article, we delineate a loosely selected cohort comprising patients with a history of early-onset breast cancer and/or a familial occurrence of cancer. The aim of this study was to gain insights into the presence of breast cancer-related gene variants in a population from a micro-region in southern Brazil, specifically the Metropolitan Region of Curitiba. This area exhibits a highly genetically mixed population, mirroring the general characteristics of the Brazilian people. METHODS: Comprehensive next-generation sequencing (NGS) multigene panel testing was conducted on 12 patients from the region, utilizing three different library preparation methods. RESULTS: Two pathogenic variants and one candidate pathogenic variant were identified: BRCA2 c.8878C>T, p.Gln2960Ter; CHEK2 c.1100del, p.Thr367Metfs15, and BRCA2 c.3482dup, p.Asp1161Glufs3. CONCLUSION: BRCA2 c.3482dup, a novel candidate pathogenic variant, previously unpublished, is reported. The prevalence of pathogenic variants in this small cohort is similar to that described in the literature. All different library preparation methods were equally proficient in enabling the detection of these variants.

Assuntos

Proteína BRCA2 , Neoplasias da Mama , Quinase do Ponto de Checagem 2 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteína BRCA2/genética , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Quinase do Ponto de Checagem 2/genética , Brasil , Pessoa de Meia-Idade , Adulto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Testes Genéticos/métodos , Testes Genéticos/normas , Predisposição Genética para Doença

RESUMO

Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

Assuntos

Hormônio Adrenocorticotrópico , Carcinoma Neuroendócrino , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Pancreáticas , Linhagem , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Masculino , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Colômbia , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/complicações , Feminino , Pessoa de Meia-Idade , Seguimentos , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Proteínas Proto-Oncogênicas/genética

RESUMO

OBJECTIVE: The aim of the study was to assess the impact of the Gamma coronavirus disease 2019 (COVID-19) variant on pregnant and postpartum women with Cardiovascular Disease (CVD). METHODS: The Influenza Epidemiological Surveillance System database (SIVEP-Gripe), a compulsory notification system for cases of Severe Acute Respiratory Syndrome (SARS), was investigated for notified cases of pregnant and postpartum women with reported CVD and SARS due to COVID-19 between February 16, 2020 and May 1, 2021 (when vaccination began), was investigated. In this retrospective cohort, two groups were formed based on symptom onset date, according to the predominance of the variants: original (group 2020) and Gamma (group 2021). Cases with missing information on the presence or absence of CVD were excluded. The comparative analysis was controlled for confounding variables. RESULTS: Among 703 COVID-19 cases notified with CVD (406 patients in 2020 and 297 patients in 2021), compared to 2020, cases in 2021 had more respiratory symptoms (90.6 % vs. 80.1 %, p < 0.001), greater ventilatory support need (75.3 % vs. 53.9 %, p < 0.001), more ICU admission (46.6 % vs. 34.3 %, p = 0.002), longer duration (20.59 ± 14.47 vs. 16.52 ± 12.98 days, p < 0.001), higher mortality (25.6 % vs. 15.5 %, p < 0.001), with more than two-times mortality likelihood in the third trimester (adjusted OR = 2.41, 95 % CI 1.50-3.88, p < 0.001) or puerperium periods (adjusted_OR = 2.15, 95 % CI 1.34-3.44, p = 0.001). CONCLUSIONS: In Brazil, pregnant and postpartum women with CVDs in the Gamma variant phase have higher morbidity and mortality than those affected by the original variant of Coronavirus-19.

Assuntos

COVID-19 , Doenças Cardiovasculares , SARS-CoV-2 , Humanos , Feminino , Gravidez , COVID-19/mortalidade , COVID-19/epidemiologia , Adulto , Estudos Retrospectivos , Doenças Cardiovasculares/mortalidade , Brasil/epidemiologia , Prognóstico , Hospitalização/estatística & dados numéricos , Complicações Infecciosas na Gravidez/virologia , Complicações Infecciosas na Gravidez/epidemiologia , Período Pós-Parto , Complicações Cardiovasculares na Gravidez , Fatores de Risco

RESUMO

The COVID-19 pandemic has been marked by novel viral variants, posing challenges to global public health. Recombination, a viral evolution mechanism, is implicated in SARS-CoV-2's ongoing evolution. The XBB recombinant lineage, known for evading antibody-mediated immunity, exhibits higher transmissibility without increased disease severity. We investigated the prevalence and genomic features of XBB in SARS-CoV-2-positive cases in Rio Grande do Sul (RS), Brazil. We sequenced 357 samples from epidemiological weeks (EW) 47/2022 to 17/2023, and included 389 publicly available sequences. Clinical and epidemiological data were obtained from DATASUS, e-SUS, and SIVEP GRIPE (data recording systems of the Brazilian Ministry of Health). Of these, 143 were classified as XBB and 586 were other Omicron lineages. In March 2023 (EW 10), XBB became dominant, accounting for 83.3% of cases. 97.7% of XBB-infected patients successfully recovered from the infection, with a low mortality rate (2.3%). Even after receiving three vaccine doses and having been previously infected, 59.5% of the patients experienced reinfection with XBB. However, for 54% of the individuals, the interval between their XBB infection and the last vaccine dose exceeded one year, potentially leading to a decline in antibody levels. In addition, we identified 90 mutations in RS circulating XBB, spread throughout the genome, notably in the Spike protein region associated with immune resistance. This study provides insights into the dynamics and impact of a recombinant variant becoming predominant for the first time in the state. Continued surveillance of SARS-CoV-2 genomic evolution is crucial for effective public health management.

Assuntos

Vacinas contra COVID-19 , COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Brasil/epidemiologia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Filogenia , Adulto Jovem , Adolescente , Genômica/métodos

RESUMO

Random mutagenesis, such as error-prone PCR (epPCR), is a technique capable of generating a wide variety of a single gene. However, epPCR can produce a large number of mutated gene variants, posing a challenge in ligating these mutated PCR products into plasmid vectors. Typically, the primers for mutagenic PCRs incorporate artificial restriction enzyme sites compatible with chosen plasmids. Products are cleaved and ligated to linearized plasmids, then recircularized by DNA ligase. However, this cut-and-paste method known as ligation-dependent process cloning (LDCP), has limited efficiency, as the loss of potential mutants is inevitable leading to a significant reduction in the library's breadth. An alternative to LDCP is the circular polymerase extension cloning (CPEC) method. This technique involves a reaction where a high-fidelity DNA polymerase extends the overlapping regions between the insert and vector, forming a circular molecule. In this study, our objective was to compare the traditional cut-and-paste enzymatic method with CPEC in producing a variant library from the gene encoding the red fluorescent protein (DsRed2) obtained by epPCR. Our findings suggest that CPEC can accelerate the cloning process in gene library generation, enabling the acquisition of a greater number of gene variants compared to methods reliant on restriction enzymes.

Assuntos

Clonagem Molecular , Biblioteca Gênica , Mutagênese , Reação em Cadeia da Polimerase , Reação em Cadeia da Polimerase/métodos , Clonagem Molecular/métodos , Vetores Genéticos/genética , DNA Polimerase Dirigida por DNA/metabolismo , DNA Polimerase Dirigida por DNA/genética , Plasmídeos/genética

RESUMO

KIAA0586 variants have been associated with a wide range of ciliopathies, mainly Joubert syndrome (JS, OMIM #616490) and short-rib thoracic dysplasia syndrome (SRTD, OMIM #616546). However, the hypothesis that this gene is involved with hydrolethalus syndrome (HSL, OMIM #614120) and orofaciodigital syndrome IV (OMIM #258860) has already been raised. Ciliopathies' clinical features are often overlapped despite differing in phenotype severity. Besides KIAA0586, HYLS1 and KIF7 are also known for being causative of ciliopathies, indicating that all three genes may have similar or converging genomic pathways. Overall, the genotypic and phenotypic spectrum of ciliopathies becomes wider and conflicting while more and more new variants are added to this group of disorders' molecular pot. In this case report we discuss the first Brazilian individual clinically diagnosed with hydrolethalus syndrome and molecular findings that demonstrate the role of KIAA0586 as a causative gene of a group of genetic disorders. Also, recent reports on individuals with intronic and exonic variants combined leading to ciliopathies support our patient's molecular diagnosis. At the same time, we discuss variable expressivity and overlapping features in ciliopathies.

Assuntos

Anormalidades Múltiplas , Cerebelo , Anormalidades do Olho , Doenças Renais Císticas , Fenótipo , Retina , Humanos , Anormalidades do Olho/genética , Anormalidades do Olho/patologia , Doenças Renais Císticas/genética , Anormalidades Múltiplas/genética , Retina/anormalidades , Retina/patologia , Retina/metabolismo , Cerebelo/anormalidades , Cerebelo/patologia , Ciliopatias/genética , Masculino , Mutação , Feminino , Proteínas de Ciclo Celular

RESUMO

The Receptor Activator Nuclear of κB Ligand (RANKL) plays an important function in immune responses, activating osteoclast cells and unchanged bone resorption, which in turn leads to bone erosion and inflammation. Genetic variants in the promoter region of the RANKL gene could lead to a higher risk of rheumatoid arthritis (RA). OBJECTIVE: To assess the association of rs9533155 (-693C>G) and rs9533156 (-643T>C) genetic variants with RA risk. METHODS: A case-control study was carried out. A total of 94 patients with RA (RA group) and 134 subjects without any rheumatologic disease (control group) were included. Genetic DNA was extracted from peripheral white blood cells (leukocytes). Genetic variant rs9533155 (-693C>G) was screened by an approach based on Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP), while rs9533156 (-643T>C) was screened using quantitative polymerase chain reaction (qPCR) with TaqMan probes. RANKL serum levels were measured by ELISA. RESULTS: For rs9533155 (-693C>G), the polymorphic homozygous genotype frequencies (CC) were higher in the RA group (p = 0.006). Individuals carrying the risk genotype presented higher levels of serum RANKL. Carriers of the polymorphic homozygous genotype in the dominant model (CC vs. CG + GG) had an increased risk of developing RA (OR: 1.8, 95% CI 1.04 to 3.1). No association between rs9533156 (-643T>C) and the haplotypes with RA risk was observed. CONCLUSION: The rs9533155 (-693C>G) genetic variant exhibits a potential role in RA risk. The studied population had no association with the rs9533156 (-643T>C) genetic variant.

Assuntos

Artrite Reumatoide , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Ligante RANK , Humanos , Artrite Reumatoide/genética , Feminino , Masculino , México , Pessoa de Meia-Idade , Estudos de Casos e Controles , Ligante RANK/genética , Ligante RANK/sangue , Adulto , Frequência do Gene , Idoso

RESUMO

[This corrects the article DOI: 10.3389/fneph.2024.1379061.].

RESUMO

Perry syndrome (PS) is a rare autosomal dominant disease characterized by parkinsonism, central hypoventilation, weight loss and depression and is caused by pathogenic mutations in the dynactin subunit 1 (DCTN1) gene (encoding p150glued protein). To date, only two cases have been reported in Latin America, specifically in Colombia and Argentina. The present study, to the best of our knowledge, reports the first recorded Mexican family with PS. The clinical features of the proband and a family history of early parkinsonism led to the suspicion of PS. The pathogenic variant NM_004082:c.212G>A, causing a (p.Gly71Glu) mutation in the p150glued protein, was identified in exon 2 of the DCTN1 gene by exome sequencing, confirming the diagnosis of PS. (p.Gly71Glu) has been previously identified in at least 4 cases of PS from different ethnic backgrounds. Genetic counseling was provided to the available family members. To clarify the impact of the (p.Gly71Glu) variant on the structure and function of the cytoskeleton-associated protein Gly rich (CAP-Gly) domain of p150glued, Glu71 mutated CAP-Gly domains were modeled and compared with the wild-type. It was hypothesized that the larger and more charged side chain of Glu may induce conformational and electrostatic changes, imposing a conformational restriction on the peptide backbone that would affect interaction with the p150glued protein partners, causing dysfunction in the dynactin protein complex.

RESUMO

Traditional descriptions of liver anatomy refer to a smooth, convex surface contacting the diaphragm. Surface depressions are recognized anatomic variants. There are many theories to explain the cause of the depressions. We discuss the theory that these are caused by hypertrophic muscular bands in the diaphragm.

RESUMO

BACKGROUND: In traditional descriptions, the upper surface of the liver is smooth and convex, but deep depressions are variants that are present in 5%-40% of patients. We sought to determine the relationship between surface depressions and the diaphragm. AIM: To use exploratory laparoscopy to determine the relationship between surface depressions and the diaphragm. METHODS: An observational study was performed in all patients undergoing laparoscopic upper gastro-intestinal operations between January 1, 2023 and January 20, 2024. A thirty-degree laparoscope was used to inspect the liver and diaphragm. When surface depressions were present, we recorded patient demographics, presence of diaphragmatic bands, rib protrusions and/or any other source of compression during inspection. RESULTS: Of 394 patients, 343 had normal surface anatomy, and 51 (12.9%) had prominent surface depressions on the liver. There was no significant relationship between the presence of surface depressions and gender nor the presence of rib projections. However, there was significant association between the presence of surface depressions and diaphragmatic muscular bands (P < 0.001). CONCLUSION: With these data, the diaphragmatic-band theory has gained increased importance over other theories for surface depressions. Further studies are warranted using cross sectional imaging to confirm relationships with intersectional planes as well as beta-catenin assays in the affected liver parenchyma.

RESUMO

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

Assuntos

Variações do Número de Cópias de DNA , Sequenciamento Completo do Genoma , Humanos , Variações do Número de Cópias de DNA/genética , Sequenciamento Completo do Genoma/economia , Sequenciamento Completo do Genoma/métodos , Brasil , Masculino , Feminino , Criança , Deficiência Intelectual/genética , Deficiência Intelectual/diagnóstico , Análise Custo-Benefício , Análise em Microsséries/economia , Análise em Microsséries/métodos , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/diagnóstico , Pré-Escolar , Anormalidades Múltiplas/genética , Anormalidades Múltiplas/diagnóstico , Países em Desenvolvimento , Adolescente , Transtornos do Neurodesenvolvimento/genética , Transtornos do Neurodesenvolvimento/diagnóstico , Testes Genéticos/economia , Testes Genéticos/métodos

RESUMO

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

Assuntos

Epilepsia do Lobo Temporal , MicroRNAs , Canal de Sódio Disparado por Voltagem NAV1.1 , Polimorfismo de Nucleotídeo Único , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , MicroRNAs/genética , Epilepsia do Lobo Temporal/genética , Epilepsia do Lobo Temporal/tratamento farmacológico , Feminino , Masculino , Brasil , Adulto , Predisposição Genética para Doença , Epilepsia Resistente a Medicamentos/genética , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Pessoa de Meia-Idade , Adulto Jovem , Genótipo , Estudos de Coortes , Alelos , Frequência do Gene , Adolescente , Estudos de Casos e Controles

RESUMO

Aminobisphosphonates (NBPs) are the first-choice medication for osteoporosis (OP); NBP treatment aims at increasing bone mineral density (BMD) by inhibiting the activity of farnesyl diphosphate synthase (FDPS) enzyme in osteoclasts. Despite its efficacy, inadequate response to the drug and side effects have been reported. The A allele of the rs2297480 (A > C) SNP, found in the regulatory region of the FDPS gene, is associated with reduced gene transcription. This study evaluates the FDPS variant rs2297480 (A > C) association with OP patients' response to alendronate sodium treatment. A total of 304 OP patients and 112 controls were enrolled; patients treated with alendronate sodium for two years were classified, according to BMD variations at specific regions (lumbar spine (L1-L4), femoral neck (FN) and total hip (TH), as responders (OP-R) (n = 20) and non-responders (OP-NR) (n = 40). We observed an association of CC genotype with treatment failure (p = 0.045), followed by a BMD decrease in the regions L1-L4 (CC = -2.21% ± 2.56; p = 0.026) and TH (CC = -2.06% ± 1.84; p = 0.015) after two years of alendronate sodium treatment. Relative expression of the FDPS gene was also evaluated in OP-R and OP-NR patients. Higher expression of the FDPS gene was also observed in OP-NR group (FC = 1.84 ± 0.77; p = 0.006) when compared to OP-R. In conclusion, the influence observed of FDPS expression and the rs2897480 variant on alendronate treatment highlights the importance of a genetic approach to improve the efficacy of treatment for primary osteoporosis.

Assuntos

Alendronato , Conservadores da Densidade Óssea , Densidade Óssea , Geraniltranstransferase , Osteoporose , Polimorfismo de Nucleotídeo Único , Falha de Tratamento , Humanos , Alendronato/uso terapêutico , Alendronato/farmacologia , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/genética , Feminino , Geraniltranstransferase/genética , Geraniltranstransferase/metabolismo , Masculino , Osteoporose/tratamento farmacológico , Osteoporose/genética , Idoso , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/uso terapêutico , Genótipo , Alelos , Estudos de Casos e Controles

RESUMO

Objective: Type 2 diabetes (T2D) and high blood pressure are the main causes of chronic kidney disease (CKD) in adulthood. Both metabolic and oxidative stresses driven by hyperglycemia as well as genetic factors have been suggested as pathogenic causes of renal failure. Some single nucleotide variants (SNVs) on gene coding KLOTHO (KL) have been implicated in several clinical scenarios including hypertension, diabetes, and cardiovascular disease. The aim of this study was to analyze the association of rs1207568 (-395G > A), rs953614 (+ 1062T > G) and rs564481 (+ 1818 C > T) SNVs with metabolic and renal function parameters in Mexican patients living with type 2 diabetes. Methods: A cross-sectional study was conducted in 637 Mexican patients with T2D, and/or hypertension without previous diagnosis of CKD. Anthropometric, metabolic, and renal function parameters were determined. Patients were genotyped for rs1207568, rs953614 and rs564481 SNVs and associations under a dominant genetic model were analyzed by logistic regression. Results: For rs9536314, G-allele showed to be protective for hypo-HDL-C, albuminuria, and CKD. Carriers of minor allele of rs564481 had low odds for high glucose levels. No differences in genotype nor allele frequencies between the patients and the reference population were observed. Conclusion: In Mexican patients living with type 2 diabetes, KL variant rs9536314 was found associated with low odds of hypo-HDL cholesterol, albuminuria and presence of CKD. Meanwhile the consensus of soluble KLOTHO measurement is reached, genetic variants in the KL gene could be considered as genetic markers for CKD susceptibility in patients at high-risk of vascular complications.

RESUMO

COVID-19 is a systemic disease caused by the etiologic agent SARS-CoV-2, first reported in Hubei Province in Wuhan, China, in late 2019. The SARS-CoV-2 virus has evolved over time with distinct transmissibility subvariants from ancestral lineages. The clinical manifestations of the disease vary according to their severity and can range from asymptomatic to severe. Due to the rapid evolution to a pandemic, epidemiological studies have become essential to understand and effectively combat COVID-19, as the incidence and mortality of this disease vary between territories and populations. This study correlated epidemiological data on the incidence and mortality of COVID-19 with frequencies of important SNPs in GWAS studies associated with the susceptibility and mortality of this disease in different populations. Our results indicated significant correlations for 11 genetic variants (rs117169628, rs2547438, rs2271616, rs12610495, rs12046291, rs35705950, rs2176724, rs10774671, rs1073165, rs4804803 and rs7528026). Of these 11 variants, 7 (rs12046291, rs117169628, rs1073165, rs2547438, rs2271616, rs12610495 and rs35705950) were positively correlated with the incidence rate, these variants were more frequent in EUR populations, suggesting that this population is more susceptible to COVID-19. The rs2176724 variant was inversely related to incidence rates; therefore, the higher the frequency of the allele is, the lower the incidence rate. This variant was more frequent in the AFR population, which suggests a protective factor against SARS-CoV-2 infection in this population. The variants rs10774671, rs4804803, and rs7528026 showed a significant relationship with mortality rates. SNPs rs10774671 and rs4804803 were inversely related to mortality rates and are more frequently present in the AFR population. The rs7528026 variant, which is more frequent in the AMR population, was positively related to mortality rates. The study has the potential to identify and correlate the genetic profile with epidemiological data, identify populations that are more susceptible to severe forms of COVID-19, and relate them to incidence and mortality.

RESUMO

Previous studies have demonstrated the essential role of the Kisspeptin/Neurokinin B/Dynorphin A (KNDy) pathway in female reproductive biology by regulating the activity of the hypothalamic-pituitary-gonadal axis. Identified loss-of-function mutations in these genes are linked to various reproductive disorders. This study investigated genetic disorders linked to mutations in the KNDy genes related to premature ovarian insufficiency (POI). A cohort of 14 Mexican POI patients underwent genetic screening using PCR-SSCP and Sanger sequencing, assessing the genetic variations' impact on protein function thereafter using multiple in silico tools. The PCR excluded extensive deletions, insertions, and duplications, while SSCP detected five genetic variants. Variations occurred in the KISS1 (c.58G>A and c.242C>G), KISS1R (c.1091A>T), PDYN (c.600C>T), and OPRK1 (c.36G>T) genes, whereas no genetic anomalies were found in NK3/NK3R genes. Each single-nucleotide variant underwent genotyping using PCR-SSCP in 100 POI-free subjects. Their allelic frequencies paralleled the patient group. These observations indicate that allelic variations in the KNDy genes may not contribute to POI etiology. Hence, screening for mutations in KNDy genes should not be a part of the diagnostic protocol for POI.

Assuntos

Kisspeptinas , Neurocinina B , Insuficiência Ovariana Primária , Humanos , Feminino , Insuficiência Ovariana Primária/genética , México , Adulto , Neurocinina B/genética , Kisspeptinas/genética , Estudos de Coortes , Polimorfismo de Nucleotídeo Único , Receptores de Kisspeptina-1/genética , Encefalinas/genética , Precursores de Proteínas

RESUMO

Hypertriglyceridemia (HTG) is a common dyslipidemia associated with an increased risk of cardiovascular disease and pancreatitis. It is well stablished that the severe cases of disease often present with an underlying genetic cause. In this study, we determined the frequency and variation spectrum of genes involved in the triglyceride metabolism in a series of Brazilian patients with severe HTG. A total of 212 patients with very high HTG, defined with fasting triglycerides (TG) ≥ 880 mg/ dL, that underwent a multi-gene panel testing were included in this research. Germline deleterious variants (i.e. Pathogenic/Likely Pathogenic (P/LP) variants) were identified in 28 out of 212 patients, reflecting an overall diagnostic yield of 13% in our cohort. Variants of unknown significance (VUS) were identified in 87 patients, and represent 80% of detected variants in this dataset. We confirm the LPL as the most frequently mutated gene in patients with severe HTG, and we had only one suspected case of familial chylomicronemia syndrome, caused by a homozygous variant in LMF1, in our cohort. Notably, we report 16 distinct and novel variants (P/LP and VUS), each of them representing a single case, not previously reported in any public databases or other studies. Our data expand our knowledge of genetic variation spectrum in patients with severe HTG in the Brazilian population, often underrepresented in public genomic databases, being also a valuable clinical resource for genetic counseling and healthcare programs in the country.

RESUMO

The current pandemic produced by SARS-CoV-2 and its variants represent an example of the one health concept in which humans and animals are components of the same epidemiologic chain. Animal reservoirs of these viruses are thus the focus of surveillance programs, to monitor their circulation and evolution in potentially new hosts and reservoirs. In this work, we report the detection of the SARS-CoV-2 Gamma variant infection in four specimens of Chaetophractus villosus (big hairy armadillo/armadillo peludo) in Argentina. In addition to the finding of a new wildlife species susceptible to SARS-CoV-2 infection, the identification of the Gamma variant three months after its last detection in humans in Argentina is a noteworthy result, which can be due to alternative non-exclusive scenarios, such as unidentified viral reservoirs, unrecognized circulation in humans or species-specific variation in incubation periods.