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Pediatric in-hospital cardiac arrest (IHCA) has been reported in 1-3% of pediatric intensive care unit (ICU) admissions and up to 6% of children admissions to the cardiac ICU. In the last 25 years, the survival to hospital discharge after pediatric IHCA has improved from 9% to 13.7% up to 35%. The improvement in outcomes was attributed in part to the application of ECMO as a rescue strategy when prolonged conventional CPR cannot restore spontaneous circulation. We report a case of a 4-month-old patient with a history of ventricular and septal defects, with left to right shunt and enlargement of left heart chambers that underwent surgery for the closure of the atrial and septal defects, and experienced complications that led to the use of ECMO in response to a prolonged cardiac arrest.

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Genetic epilepsy with febrile seizures plus (GEFS+) is an autosomal dominant disorder with febrile or afebrile seizures that exhibits phenotypic variability. Only a few variants in SCN1A have been previously characterized for GEFS+, in Latin American populations where studies on the genetic and phenotypic spectrum of GEFS+ are scarce. We evaluated members in two multi-generational Colombian Paisa families whose affected members present with classic GEFS+. Exome and Sanger sequencing were used to detect the causal variants in these families. In each of these families, we identified variants in SCN1A causing GEFS+ with incomplete penetrance. In Family 047, we identified a heterozygous variant (c.3530C > G; p.(Pro1177Arg)) that segregates with GEFS+ in 15 affected individuals. In Family 167, we identified a previously unreported variant (c.725A > G; p.(Gln242Arg)) that segregates with the disease in a family with four affected members. Both variants are located in a cytoplasmic loop region in SCN1A and based on our findings the variants are classified as pathogenic and likely pathogenic, respectively. Our results expand the genotypic and phenotypic spectrum associated with SCN1A variants and will aid in improving molecular diagnostics and counseling in Latin American and other populations.

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Introducción. La fractura de pene es una emergencia urológica rara, se desconoce la incidencia real dado el subregistro causado por la reducida consulta de los pacientes, resultado del embarazoso contexto. En Estados Unidos alcanza un 38% donde la etiología de índole sexual predomina. En Colombia hay escasos reportes publicados. El diagnóstico de esta entidad es netamente clínico. El objetivo de este trabajo es reportar una evolución satisfactoria en términos de función miccional y eréctil en un paciente sometido a reconstrucción cavernosa y uretral temprana en rotura bilateral de origen traumático mediante una técnica quirúrgica poco convencional, de acuerdo con lo hallado en la literatura. Presentación del caso. Paciente masculino de 30 años, previamente sano, quien consultó al servicio de urgencias por uretrorragia, edema y dolor peneano secundario a trauma contuso del mismo durante relación sexual. El reporte ecográfico mostró disrupción en túnica albugínea del cuerpo esponjoso, hematoma y aparente transección uretral; se realizó exploración quirúrgica 6 horas después, con evidencia de fractura de cuerpos cavernosos, laceración del 40% de la circunferencia, transección completa de la uretra y cuerpo esponjoso. Se realizó rafia de cuerpos cavernosos y uretroplastia término terminal de uretra bulbar, con evolución clínica satisfactoria. Discusión. La reconstrucción quirúrgica en menos de 24 horas en fractura de pene disminuye significativamente la estancia hospitalaria y complicaciones precoces; asimismo, desciende el riesgo de disfunción eréctil, erecciones dolorosas y problemas miccionales. No hay publicaciones que comparen resultados a largo plazo entre los dos abordajes quirúrgicos. Conclusiones. La fractura de pene es una patología poco frecuente con diagnóstico clínico, la cual debe manejarse de manera temprana por cualquier urólogo y, en caso de ser posible, con experiencia reconstructiva y excelentes resultados en la función sexual y miccional.

Introduction. Penile fracture is a rare urological emergency, the real incidence is unknown given the underreporting caused by the reduced consultation of patients, resulting from the embarrassing context. In the United States it reaches 38%, where sexual etiology predominates. In Colombia there are few published reports. The diagnosis of this entity is purely clinical. The aim of this work is to report a satisfactory evolution in terms of voiding and erectile function in a patient who underwent early cavernous and urethral reconstruction in bilateral rupture of traumatic origin by means of an unconventional surgical technique, in accordance with what has been found in the literature. Case Presentation. A 30-year-old male patient, previously healthy, consulted the emergency department for urethrorrhagia, edema and penile pain secondary to blunt trauma to the penis during sexual intercourse. The ultrasound report showed disruption in the tunica albuginea of the corpus spongiosum, hematoma and apparent urethral transection; surgical exploration was performed 6 hours later, with evidence of fracture of the corpora cavernosa, laceration of 40% of the circumference, complete transection of the urethra and corpus spongiosum. Sutures to the corpora cavernosa and end-to-end urethroplasty of the bulbar urethra were performed, with satisfactory clinical evolution. Discussion. Surgical reconstruction in less than 24 hours in penile fractures significantly reduces hospital stay and early complications; it also reduces the risk of erectile dysfunction, painful erections and voiding problems. There are no publications comparing long-term results between the two surgical approaches. Conclusions. Penile fracture is a rare pathology with clinical diagnosis, which should be managed early by any urologist and, if possible, with reconstructive experience and excellent results in sexual and voiding function.

Introdução. A fratura peniana é uma emergência urológica rara, a real incidência é desconhecida dada a subnotificação causada pela reduzida consulta de pacientes, resultado do contexto constrangedor. Nos Estados Unidos chega a 38% onde predomina a etiologia de natureza sexual. Na Colômbia há poucos relatórios publicados. O diagnóstico desta entidade é puramente clínico. O objetivo deste trabalho é relatar uma evolução satisfatória da função miccional e erétil em um paciente submetido à reconstrução cavernosa e uretral precoce em ruptura bilateral de origem traumática por meio de técnica cirúrgica não convencional, de acordo com o que foi encontrado na literatura. Apresentação do caso. Paciente do sexo masculino, 30 anos, previamente saudável, procurou o pronto-socorro por uretrorragia, edema e dor peniana secundária a trauma contuso durante a relação sexual. O relatório do ultrassom mostrou ruptura na túnica albugínea do corpo esponjoso, hematoma e transecção uretral aparente; a exploração cirúrgica foi realizada 6 horas depois, com evidência de fratura dos corpos cavernosos, laceração de 40% da circunferência, transecção completa da uretra e corpo esponjoso. Foram realizadas ráfia dos corpos cavernosos e uretroplastia término-terminal da uretra bulbar, com evolução clínica satisfatória. Discussão. A reconstrução cirúrgica em menos de 24 horas nas fraturas penianas reduz significativamente o tempo de internação e as complicações precoces. Da mesma forma, diminui o risco de disfunção erétil, ereções dolorosas e problemas de micção. Não há publicações comparando os resultados a longo prazo entre as duas abordagens cirúrgicas. Conclusões. A fratura peniana é uma patologia rara com diagnóstico clínico, que deve ser tratada precocemente por qualquer urologista e, se possível, com experiência reconstrutiva e excelentes resultados na função sexual e miccional.

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X-linked adrenal hypoplasia congenita is a rare cause of primary adrenal insufficiency. Mutations in the NR0B1 gene cause a loss of function in the DAX1 receptor, which activates genes involved in the development and function of the hypothalamic-pituitary-gonadal axis. Objective: To describe a case of adrenal hypoplasia congenita secondary to a mutation in the NR0B1 gene and identified the differential diagnoses of the pediatric patient with adrenal insufficiency and hypogonadotropic hypogonadism. Clinical Case: A 4-year-old male patient with no relevant history and from a rural area was admitted to the emergency room due to a 15-days of emesis, asthenia, adynamia, myalgia, and ataxic gait. On the physical examination, hypotension, hyponatremia, and hyperkalemia, as well as mucosal hyperpigmentation and bilateral cryptorchidism were observed, therefore, adrenal crisis was diagnosed, starting fluid resuscitation with saline solution, hydrocortisone, and fludrocortisone, which stabilized the patient. Adrenal hyperplasia congenita, innate metabolic error, and infectious or autoimmune etiology were ruled out as etiology. A clinical exome test was performed which iden tified the variant c.1275A > T; p.Arg425Ser (Transcript ENST00000378970.5) in the NR0B1 gene consistent with X-linked adrenal hypoplasia congenita. Management of the patient continued with glucocorticoids and mineralocorticoids with favorable clinical course at 7 years of follow-up. Con clusion: A novel pathogenic variant associated with X-linked adrenal hypoplasia is described. Variants in the NR0B1 gene should be a differential diagnosis in a male patient with the association of primary adrenal insufficiency and hypogonadism.

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INTRODUCTION: Psoriasis is a chronic inflammatory dermatosis, a with variable clinical presentation and whose multifactorial etiology carries an essential genetic component. Multiple genetic variations associated with psoriasis have been described around the world. However, these variants are unknown among the Colombian population. This study aimed to evaluate the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene and its ssociation with the development of psoriasis in a Colombian population. METHODS: An observational, unmatched, case-control study was performed, including 51 patients with psoriasis and 151 population controls, all with self-reported Paisa ancestry (from the Antioquia region). All individuals were genotyped for the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene, and its association with psoriasis was pursued. Both groups were demographically characterized, and cases were also assessed for clinical variables. RESULTS: Through the allelic association analysis, cases were found to have a lower frequency of the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene than controls; 5% versus 22.67%, respectively. There were no significant differences in age or sex. We also found that psoriasis vulgaris was the most common variant (78%), that about half of the cases had nail psoriasis (56%), 19.6% had psoriatic arthritis, and that 45% had some comorbidity. CONCLUSIONS: The results obtained from this study confirm that carriers of the single nucleotide polymorphism rs10930046 (His460Arg) in the IFIH1 gene have a decreased risk of developing psoriasis.

INTRODUCCIÓN: La psoriasis es una dermatosis inflamatoria crónica, con presentación clínica variable y cuya etiología involucra un componente genético importante. Alrededor del mundo se han descrito múltiples variaciones genéticas asociadas a la enfermedad. Sin embargo, en población colombiana se desconocen estas variantes. En este estudio se evalúa el polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 y su asociación con el desarrollo de psoriasis en población colombiana. Además, se caracteriza a los individuos demográfica y clínicamente. MÉTODOS: Se realizó un estudio observacional de casos y controles, no pareado, que incluyó 51 individuos con psoriasis y 151 controles poblacionales, todos de ancestría paisa (proveniente de la región de Antioquia) auto reportada. A todos los individuos se les realizó genotipificación del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 y se les determinó la asociación con la enfermedad. Se caracterizaron demográficamente ambos grupos y los casos clínicamente. RESULTADOS: Se encontró que los casos presentaron una menor frecuencia del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1 en relación a los controles, 5 versus 22,67% respectivamente, con un análisis de asociación alélico. No hubo diferencias significativas en edad ni en sexo. La psoriasis vulgar fue la variante de presentación más común (78%). Alrededor de la mitad de los casos presentaron psoriasis ungular (56%), en menor frecuencia artritis psoriásica (19,6%) y el 45% de los casos tuvo alguna comorbilidad. CONCLUSIONES: Los resultados obtenidos confirman que los portadores del polimorfismo de nucleótido único rs10930046 (His460Arg) en el gen IFIH1, presentan un riesgo disminuido de desarrollar psoriasis.

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PURPOSE: Our purpose was to describe the phenotypic features and test for association of genes GRIN2A, RBFOX1 and RBFOX3 with rolandic epilepsy in patients from Colombia. METHODS: Thirty patients were enrolled. A structured interview was applied. In addition, saliva samples were collected from the patients and their parents. One polymorphism in each of GRIN2A, RBFOX1 and RBFOX3 genes was tested. RESULTS: The average age at onset was 5.3 years. Almost half the sample presented prolonged seizures (>5 minutes); although the majority of the patients presented their seizures only while asleep, over a quarter presented them only while awake. The most frequent comorbidity was the presence of symptoms compatible with attention-deficit hyperactivity disorder (ADHD). Personal history of febrile seizures and parasomnias were equally frequent (20%). Family history of any type of epilepsy was reported in 80% of the patients, followed by migraine (73.3%) and poor academic performance (63.3%). About half the sample reported sleepwalking in parents or sibs. Most patients had received pharmacologic treatment. We found no association of rolandic epilepsy with the single nucleotide polymorphisms tested. CONCLUSIONS: Our rolandic epilepsy cohort presents clinical features clearly different from other cohorts. For instance, age at onset is much earlier in our set of patients, and personal and family history of febrile seizures as well as parasomnias are highly prevalent in our sample. No association of rolandic epilepsy with variants at the 3 genes tested was found. This lack of association may reflect the high genetic heterogeneity of the epilepsies.

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OBJECTIVES: RNASEH1 gene has recently been associated with type 1 diabetes (T1D) in Colombia. The purpose of this study was to fine mapping the putative functional variant in RNASEH1 and testing its interaction with HLA tagSNPs. METHODS: Two-hundred nuclear families with T1D were included in this study. Probands were tested for GAD65 and IA-2 autoantibodies. Genotyping was performed using 20 coding tagSNPs uncovered through Sanger sequencing (N = 96), in addition to 23 tagSNPs chosen from 1000genomes to cover the extent of the gene region. Also, 45 tagSNPs for classic HLA alleles associated with T1D were also genotyped. The transmission disequilibrium test (TDT) was used to test for association and a multiple testing correction was made using permutation. Interaction between RNASEH1 variants and HLA was evaluated by means of the M-TDT test. RESULTS: We identified 20 variants (15 were novel) in the 96 patients sequenced. None of these variants were in linkage disequilibrium. In total, 43 RNASEH1 variants were genotyped in the 200 families. Association between T1D and rs7607888 was identified (P = .002). Haplotype analysis involving rs7607888 variant revealed even stronger association with T1D (most significative P = .0003). HLA tagSNPs displayed stronger associations (OR = 6.39, 95% CI = 4.33-9.44, P-value = 9.74E-28). Finally, we found several statistically significant interactions of HLA variants with rs7607888 (P-value ranged from 8.77E-04 to 5.33E-12). CONCLUSION: Our results verify the association of rs7607888 in RNASEH1 gene with T1D. It is also shown in the interaction between RNASEH1 and HLA for conveying risk to T1D in Northwest Colombia. Work is underway aiming to identify the actual classic HLA alleles associated with the tagSNPs tested here.

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Theory-free characterizations of experimental systems miss normative and conceptual components that sometimes are crucial to understanding their historical development. In the following paper, we show that these components may be part of the intrinsic capacities of experimental systems themselves. We study a case of non-exploratory and theory-oriented research in experimental neuroscience that concerns the construction of free-viewing as an experimental system to test one particular pre-existing hypothesis, the Temporal Correlation Hypothesis (TCH), at a laboratory in Santiago de Chile, during 2002-2008. We show that the system does not take well-formulated pre-existing predictions or hypotheses to test them directly, but re-creates them and re-signifies them in terms that are not implied by the theoretical background from which they originally derived. Therefore, we conclude that there is a sui generis way in which experimental systems produce proper theoretical knowledge.

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BACKGROUND: Type 1 diabetes (T1D) is a complex disease with a higher incidence in Europeans than other populations. The Colombians Living in Medellin (CLM) is admixed with ancestry contributions from Europeans, Native Americans (NAT) and Africans (AFR). AIM: Our aim was to analyze the genetic admixture component at candidate T1D loci in Colombian individuals with the disease. METHODS: Seventy-four ancestry informative markers (AIMs), which tagged 41 T1D candidate loci/genes, were tested by studying a cohort of 200 Northwest Colombia diseased individuals. T1D status was classified by testing for glutamic acid decarboxylase (GAD-65 kDa) and protein tyrosine-like antigen-2 auto-antibodies in serum samples. Candidate loci/genes included HLA, INS, PTPN22, CTLA4, IL2RA, SUMO4, CLEC16A, IFIH1, EFR3B, IL7R, NRP1 and RNASEH1, amongst others. The 1,000 genome database was used to analyze data from 94 individuals corresponding to the reference CLM. As the data did not comply with a normal distribution, medians were compared between groups using the Mann-Whitney U-test. RESULTS: Both T1D patients and individuals from CLM displayed mainly European ancestry (61.58 vs 62.06) followed by Native American (27.34 vs 27.46) and to a lesser extent the AFR ancestry (10.28 vs 10.65) components. However, compared to CLM, ancestry of T1D patients displayed a decrease of NAT ancestry at gene EFR3B (24.30 vs 37.10) and an increase at genes IFIH1 (32.07 vs 14.99) and IL7R (52.18 vs 39.18). Also, for gene NRP1 (36.67 vs 0.003), we observed a non-AFR contribution (attributed to NAT). Autoimmune patients (positive for any of two auto-antibodies) displayed lower NAT ancestry than idiopathic patients at the MHC region (20.36 vs 31.88). Also, late onset patients presented with greater AFR ancestry than early onset patients at gene IL7R (19.96 vs 6.17). An association analysis showed that, even after adjusting for admixture, an association exists for at least seven such AIMs, with the strongest findings on chromosomes 5 and 10 (gene IL7R, P = 5.56 × 10-6 and gene NRP1, P = 8.70 × 10-19, respectively). CONCLUSION: Although Colombian T1D patients have globally presented with higher European admixture, specific T1D loci have displayed varying levels of Native American and AFR ancestries in diseased individuals.

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INTRODUCTION: The neuroendocrine differentiation in prostate cancer is a rare entity that may occur as de novo, or as a result of treatment with androgen deprivation. It is characterized by its rapid progression and poor prognosis, without elevation of the prostate specific antigen (PSA), which is why it is often diagnosed by biopsy of a site of metastasis; there are no established treatment regimens. In this case, metastasis was presented as implantation to a laparoscopic port. These implantations subsequent to laparoscopic procedures in prostate cancer are very rare, with an incidence between 0.09 and 0.7%. The exact pathogenesis of the tumor implantation at the insertion site is not clear, there are several theories. MATERIALS AND METHODS: We describe the case of a 53-year-old patient with a diagnosis of prostate adenocarcinoma who underwent laparoscopic radical prostatectomy plus lymphadenectomy, staged as PT3BN0 (0/6) M0R1 Gleason 4 + 5. The patient never had negative PSA levels after the treatment, and presented elevation of the same, so radiotherapy was performed at a dose of 66 Gy plus antiandrogen deprivation therapy with leuprolide acetate for 30 months, with a decrease in PSA to 0.011 ng/ml, which remained stable. After 3 months of hormonal therapy, he presented with an umbilical mass on the scar of the laparoscopic port; ultrasound and computed tomography were performed, showing a solid mass dependent of the umbilical upper edge with a defect in the abdominal wall of 3 cm, as well as hepatic nodules suggestive of metastatic lesions and peritoneal implantations. RESULTS: A biopsy of the abdominal wall lesion was performed, documenting poorly differentiated carcinoma with an immune-profile consistent with neuroendocrine carcinoma; immunohistochemistry showed strong and diffuse positivity with cytokeratin cocktail and chromogranin. In conjunction with oncology, treatment with chemotherapy was decided. He received six cycles of cisplatin and etoposide, with progression of his disease and death seven months after diagnosis. CONCLUSIONS: Prostate cancer with neuroendocrine differentiation is a rare entity, usually occurring in the castration resistance stage, with poor prognosis and survival of less than 1 year. It presents as clinical and radiological progression without elevation of the PSA. Although it is very rare, the possible causes include tumor implantation in laparoscopic ports and/or open surgery scars, so caution and certain precautions must be taken when performing radical prostatectomy. In case of suspecting a tumor with neuroendocrine differentiation, biopsy and immunohistochemistry studies should be performed in order to clarify the diagnosis and provide a multimodal treatment based on surgery, radiotherapy and chemotherapy.

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BACKGROUND: Sleep deprivation commonly increases seizure frequency in patients with genetic generalized epilepsy, though it is unknown whether there is an increased prevalence of sleepwalking or sleep paralysis in genetic generalized epilepsy patients. Establishing this could provide insights into the bio-mechanisms or genetic architecture of both disorders. The aim of this study was to determine the prevalence of sleepwalking and sleep paralysis in a cohort of patients with genetic generalized epilepsy and their relatives in extended families. METHODS: A structured interview based on International League Against Epilepsy (ILAE) and International Classification of Sleep Disorders (ICSD-3) criteria was applied to 67 index cases and their relatives to determine genetic generalized epilepsy subtypes and assess the occurrence of sleepwalking or sleep paralysis. Bivariate analysis was performed using chi-square and Fisher exact tests. RESULTS: The prevalence of sleepwalking and sleep paralysis was 15.3% (95% confidence interval 12.1-18.9) and 11.7% (95% confidence interval 8.7-15.3), respectively. Unusually, no sleepwalkers were found among individuals displaying epilepsy with generalized tonic-clonic seizures. Approximately a quarter of the patients had either parasomnia or genetic generalized epilepsy. Over half the genetic generalized epilepsy families had at least 1 individual with sleepwalking, and more than 40% of the families had one individual with sleep paralysis. CONCLUSION: The prevalence of sleepwalking or sleep paralysis is reported for individuals with genetic generalized epilepsy and their relatives. The co-existence of either parasomnia in the genetic generalized epilepsy patients and the co-aggregation within their families let suggest that shared heritability and pathophysiological mechanisms exist between these disorders. We hypothesize that sleepwalking/sleep paralysis and genetic generalized epilepsy could be variable expression of genes in shared pathways.

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BACKGROUND: The global epidemiology of type 1 diabetes (T1D) is not yet well known, as no precise data are available from many countries. T1D is, however, characterized by an important variation in incidences among countries and a dramatic increase of these incidences during the last decades, predominantly in younger children. In the United States and Europe, the increase has been associated with the gross domestic product (GDP) per capita. In our previous systematic review, geographical variation of incidence was correlated with socio-economic factors. AIM: To investigate variation in the incidence of T1D in age categories and search to what extent these variations correlated with the GDP per capita. METHODS: A systematic review was performed to retrieve information about the global incidence of T1D among those younger than 14 years of age. The study was carried out according to the PRISMA recommendations. For the analysis, the incidence was organized in the periods: 1975-1999 and 2000-2017. We searched the incidence of T1D in the age-groups 0-4, 5-9 and 10-14. We compared the incidences in countries for which information was available for the two periods. We obtained the GDP from the World Bank. We analysed the relationship between the incidence of T1D with the GDP in countries reporting data at the national level. RESULTS: We retrieved information for 84 out of 194 countries around the world. We found a wide geographic variation in the incidence of T1D and a worldwide increase during the two periods. The largest contribution to this increase was observed in the youngest group of children with T1D, with a relative increase of almost double when comparing the two periods (P value = 2.5 × e-5). Twenty-six countries had information on the incidence of T1D at the national level for the two periods. There was a positive correlation between GDP and the incidence of T1D in both periods (Spearman correlation = 0.52 from 1975-1999 and Spearman correlation = 0.53 from 2000-2017). CONCLUSION: The incidence increase was higher in the youngest group (0-4 years of age), and the highest incidences of T1D were found in wealthier countries.

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Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.

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Resumen Introducción. La región del antígeno leucocitario humano (Human Leukocyte Antigen, HLA) se ha asociado claramente con enfermedades autoinmunitarias, como la diabetes mellitus de tipo 1. Los polimorfismos representativos de un solo nucleótido (tag Single Nucleotide Polymorphism, tag SNP) constituyen una forma alternativa de evaluar los alelos clásicos del HLA. En la población europea se ha reportado un grupo de tag SNP para múltiples alelos clásicos relacionados con la predisposición o la resistencia frente a dicha enfermedad. Objetivo. Validar la metodología basada en los tag SNP enfocada en la inferencia de alelos HLA clásicos, y evaluar su asociación con la diabetes mellitus de tipo 1 en una muestra de familias antioqueñas. Materiales y métodos. Se estudió una muestra de 200 familias antioqueñas con uno a dos hijos afectados por diabetes mellitus de tipo 1. Se genotipificaron 13 SNP mediante el ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction) con cuatro iniciadores, o mediante la PCR-RFLP (PCR-Restriction Fragment Length Polymorphism). Además, se evaluó la validez de los tag SNP de 1.000 genomas reportados en europeos en una muestra de 60 individuos de la población colombiana de Medellín. Se hicieron las pruebas de desequilibrio de la transmisión, de desequilibrio de ligamiento y de equilibrio de Hardy-Weinberg. Resultados. En la población de estudio no se encontró suficiente desequilibrio de ligamiento entre los SNP y los alelos clásicos evaluados, por lo cual no fue posible inferir los alelos clásicos del HLA para el conjunto de familias con diabetes mellitus de tipo 1. El estudio de asociación evidenció que esta región aporta factores tanto de riesgo como de protección para el desarrollo de la enfermedad. Los tag SNP apropiados para la muestra de estudio se determinaron usando los SNP ubicados en la región HLA en la base de datos del 1000 Genomes Project en la mencionada población. Conclusiones. Los patrones de desequilibrio de ligamiento en la población estudiada fueron diferentes a los reportados para la población europea. A pesar de esto, se encontró evidencia clara sobre el papel de la región HLA en el riesgo de padecer diabetes mellitus de tipo 1 en la población de estudio.

abstract Introduction: The HLA region strongly associates with autoimmune diseases, such as type 1 diabetes. An alternative way to test classical HLA alleles is by using tag SNP. A set of tag SNP for several classical HLA alleles has been reported as associated with susceptibility or resistance to this disease in Europeans. Objective: We aimed at validating the methodology based on tag SNP focused on the inference of classical HLA alleles, and at evaluating their association with type 1 diabetes mellitus in a sample of 200 families from Antioquia. Materials and methods: We studied a sample of 200 families from Antioquia. Each family had one or two children with T1D. We genotyped 13 SNPs using tetra-primer ARMS-PCR or PCRRFLP. In addition, we tested the validity of the tag SNP reported for Europeans in 60 individuals from a population of Colombians living in Medellín (CLM) from the 1000 Genomes Project database. Statistical analyses included the Hardy-Weinberg equilibrium, the transmission disequilibrium and the linkage disequilibrium tests. Results: The linkage disequilibrium was low in reported tag SNP and classical HLA alleles in this CLM population. Association analyses revealed both risk and protection factors to develop type 1 diabetes mellitus. Appropriate tag SNPs for the CLM population were determined by using the genotype information available in the 1000 Genome Project database. Conclusions: Although linkage disequilibrium patterns in this CLM population were different from those reported in Europeans, we did find strong evidence of the role of HLA in the development of type 1 diabetes mellitus in the study population.

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INTRODUCTION: There is strong evidence that both genetic and environmental factors may affect the periodontal clinical status. However, epidemiological evidence on the association between Vitamin D Receptor (VDR) polymorphisms and Chronic Periodontitis (CP) has been inconsistent. AIM: The focus of this study was to identify if a possible association between VDR Single-Nucleotide Polymorphisms (SNPs) may be implicated in the aetiopathogenesis of CP in Colombian population. MATERIALS AND METHODS: One hundred and ten CP patients and 50 Healthy Controls (HC) were recruited. Periodontal status was assessed based on probing depth, clinical attachment level, extent, and severity of periodontal breakdown. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify the VDR rs7975232, rs1544410, rs2228570, and rs731236 SNPs from saliva samples. Odds Ratios (ORs) along with their 95% Confidence Intervals (CIs) were computed to compare the distribution of genotypes/alleles between HC and CP patients, alongside with analysis of Linkage Disequilibrium (LD) and haplotype associations between SNPs. Also, an analysis of the interaction between genetic findings and those significant demographic factors was performed for all SNPs. RESULTS: There was no association neither between the different genotypes/allele frequencies nor haplotypes and CP. Similarly, no significant differences in extent or severity amongst genotype/allele groups were observed. Even so, interaction analysis revealed significant synergistic interactions between each SNP and age associated with the disease status. CONCLUSION: Although these results do not support that VDR SNPs could be identified as independent risk predictor variables for CP in the Colombian population, synergistic biological interactive effects of all these SNPs related to age might play a significant role in the pathogenic pathways of CP.

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Resumen: la hiperplasia adrenal congénita corresponde a un grupo de enfermedades heredadas con defectos enzimáticos que pueden comprometer la biosíntesis del cortisol. La deficiencia de la enzima 3β-hidroxiesteroide deshidrogenasa tipo 2 es una causa rara de este defecto en la que el desarrollo genital masculino se encuentra alterado y presenta una virilización leve en las mujeres afectadas. En humanos se han descrito dos isoenzimas, la tipo I y la tipo II, codificadas por los genes HSD3B1 y HSD3B2, respectivamente, con una distribución tisular específica.Los programas de tamización de la hiperplasia adrenal congénita reportan elevación paradójica de la 17-hidroxiprogesterona secundaria al efecto periférico de la 3β-hidroxiesteroide deshidrogenasa tipo 1, isoenzima de la 3β-hidroxiesteroide deshidrogenasa tipo 2, que tiene una constante de Michaelis menor con el sustrato.A pesar de la baja prevalencia el estudio de este defecto ha tenido importantes avances en cuanto a la información molecular y el diagnóstico hormonal, datos que han sido respaldados por la identificación de la alteración genética y han disminuido la posibilidad del sobrediagnóstico; evento que se estaba presentado frecuentemente con los puntos de cortes establecidos inicialmente para el diagnósticode la enfermedad, sobre todo en sus formas leves.

Abstract: the congenital adrenal hyperplasia corresponds to a group of inherited diseases with enzyme defects that alter the cortisol biosynthesis. The 3β-hydroxysteroid dehydrogenase type 2 deficiency is a rare cause of this defect, where the male genital development is altered but little virilization in affected women is present. In humans two isoenzymes have been described, type I and type II, coded by HSD3B2 and HSD3B1 genes, respectively, and with specific tissuedistribution. The screening programs to congenital adrenal hyperplasia report paradoxical elevation of 17-hydroxyprogesterone secondary to peripheral effect of 3β-hydroxysteroid dehydrogenase type 1, an isoenzyme of 3β-hydroxysteroid dehydrogenase type 2. Type 1 has a lower Michaelis constant with the substrate; additional condition that relates with the paradoxical effect of the 17-hydroxyprogesterone.Besides the low prevalence, the study of this defect has had important progress about molecular information and hormonal diagnosis, data that has been confirmed with the identification of genetic alteration in the described gene, reducing the possibility of overdiagnosis; an event that was showing frequently with the initially cut-point stablished especially for milder forms of the disease.

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BACKGROUND: Protein tyrosine phosphatase, non-receptor type 22 (lymphoid) (PTPN22), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), and interferon induced with helicase C domain 1 (IFIH1) are among the confirmed type 1 diabetes (T1D) susceptibility genes in several populations. The aim of this study was to evaluate the role of PTPN22, CTLA4, and IFIH1 gene variants in the development of T1D in a Colombian population. METHODS: Associations of PTPN22, CTLA4, and IFIH1 variants with T1D were investigated in a sample of 197 nuclear families, including 205 affected children, in the Colombian population. Three to four single nucleotide polymorphisms (SNPs) were analyzed per gene: rs2476600, rs2476601, rs1217418, and rs2488457 for PTPN22; rs1990760, rs3747517, and rs10930046 for IFIH1; and rs231775, rs3087243, and rs231779 for CTLA4. A transmission disequilibrium test was performed for the global sample, in addition to stratified analysis considering autoimmunity, age at onset, and parent of origin. Haplotypes per gene were also analyzed. RESULTS: There was no significant transmission distortion for CTLA4. Conversely, SNPs rs10930046 (IFIH1) and rs2476601 (PTPN222) exhibited significant transmission distortion of the C and T alleles, respectively, from parents to affected children (odds ratio [OR] 0.57 and 1.83, respectively). In addition, decreased transmission of the C allele for rs10930046 occurred preferentially from mothers. Stratification analysis revealed that this association was maintained in individuals who were positive for autoantibodies and in those with an age of diagnosis <5 years. CONCLUSION: The results show that IFIH1 and PTPN22 are associated with T1D in Colombian families.

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The main genetic factor related to HIV-1 resistance is the CCR5-Δ32 mutation; however, the homozygous genotype is uncommon. The CCR5-Δ32 mutation along with single nucleotide polymorphisms (SNPs) in the CCR5 promoter and the CCR2-V64I mutation have been included in seven human haplogroups (HH) previously associated with resistance/susceptibility to HIV-1 infection and different rates of AIDS progression. Here, we determined the association of the CCR5 promoter SNPs, the CCR5-Δ32 mutation, CCR2-V64I SNP, and HH frequencies with resistance/susceptibility to HIV-1 infection in a cohort of HIV-1-serodiscordant couples from Colombia. Seventy HIV-1-exposed, but seronegative (HESN) individuals, 57 seropositives (SP), and 112 healthy controls (HC) were included. The CCR5-Δ32 mutation and CCR2-V64I SNP were identified by PCR, and the CCR5 promoter SNPs were evaluated by sequencing. None of the individuals exhibited a homozygous Δ32 genotype; the CCR2-I allele was more frequent in HESN (34%) than HC (23%) (p=0.039, OR=1.672). The frequency of the 29G allele was higher in SP than HC (p=0.003, OR=3). HHF2 showed a higher frequency in HC (19%) than SP (9%) (p=0.027), while HHG1 was more frequent in SP (11.1%) than in HC (4.2%) (p=0.019). The AGACCAC-CCR2-I-CCR5 wild-type haplotype showed a higher frequency in SP (14.2%) than in HC (3.7%) (p=0.001). In conclusion, the CCR5-Δ32 allele is not responsible for HIV-1 resistance in this HESN group; however, the CCR2-I allele could be protective, while the 29G allele might increase the likelihood of acquiring HIV-1 infection. HHG1 and the AGACCAC-CCR2-I-CCR5 wild-type haplotype might promote HIV-1 infection while HHF2 might be related to resistance. However, additional studies are required to evaluate the implications of these findings.

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Introducción: se describen los casos de dos pacientes con fibrosis quística (FQ) con alcalosis metabólica hipoclorémica: uno con diagnóstico de novo y otro con una recaída. Casos clínicos: pacientes de 6 y 9 meses que consultan por tos, fiebre y disnea. El primero con síndrome bronco-obstructivo recurrente (SBOR), el segundo con FQ conocida. Examen físico: dificultad respiratoria, deshidratación y desnutrición. Gasometría: alcalosis metabólica, hipokalemia e hipocloremia graves. Se tratan con cloruro de sodio y potasio. Hay mejoría del desequilibrio electrolítico y del estado ácido-base. No se documentan pérdidas renales o gastrointestinales de cloro y se diagnostica síndrome pseudo-Bartter. Los electrólitos en sudor de ambos pacientes son elevados. Se diagnostica alcalosis metabólica por FQ. Conclusión: la alcalosis metabólica puede ser la manifestación inicial en niños con SBOR y talla baja con sospecha de FQ; igualmente puede hacer parte de una exacerbación aguda en pacientes conocidos con FQ. Con su reconocimiento y tratamiento oportunos disminuye la morbilidad.

Introduction: We describe the cases of two patients with hypochloremic metabolic alkalosis either as the initial presentation of cystic fibrosis (case 1) or as part of a second cystic fibrosis exacerbation (case 2). Clinical cases: Two patients, 6 and 9 months old, were brought to the hospital because of cough, fever, and dyspnea. The first had a syndrome of recurrent bronchial obstruction, without the diagnosis of CF on admission. Both presented with difficulty for breathing, dehydration, and malnutrition. Arterial blood gases showed metabolic acidosis, hypokalemia, and severe hypochloremia. Treatment with sodium chloride and potassium improved their electrolyte balance and acid-base status. They did not have renal or gastrointestinal losses of chloride. CF and pseudo-Barter's syndrome were diagnosed. Conclusion: Metabolic alkalosis can be the initial manifestation of CF in infants with recurrent bronchiolitis and short stature suspicious of having CF. It can also be the expression of an acute exacerbation in patients with known CF. Opportune diagnosis and treatment are important to decrease morbidity.

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Febrile seizures and epilepsy are believed to be linked and some forms of epilepsy are associated with a history of febrile seizures (FS). Linkage analysis to seven known loci for FS and/or genetic epilepsy with febrile seizures plus (GEFS plus) was performed in a small Colombian family. Short tandem repeat (STR) markers were genotyped and two-point linkage analysis and haplotype reconstruction were conducted. A maximum LOD score of 0.75 at marker D8S533 for FEB1 at a recombination fraction (θ) of 0 and a segregating haplotype were identified. FEB1 was the first locus to be associated with FS and this is the second report to describe this association. Two genes in this region, CRH and DEPDC2, are good putative candidate genes that may play a role in FS and/or GEFS plus.

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