Sample records for HETERCIGOTOS (heterozygotes)
from WorldWideScience.org

Sample records 1 - 17 shown.



1

Fenotipo y genotipo del doble heterocigoto para δβ Talasemia/βIVSII-849 Talasemia en una familia venezolana./ Phenotyping and genotyping studies in a family with the compound heterozygosity δβ thalassemia/βIVSII-849 thalassemia

Bravo-Urquiola, Martha; Arends, Anabel; Montilla, Silvia; Guevara- I, José María; García, Gloria; Álvarez, Maritza; Castillo, Omar
2006-06-01

Resumen en español El propósito es una niña de 2 años de edad, con anemia hemolítica severa, transfusión dependiente, quien presenta un cuadro clínico sugestivo de β talasemia mayor. Al examen físico se constata la presencia de esplenomegalia, malformaciones óseas y retardo en el crecimiento. La presencia de las distintas hemoglobinas: Hb A, Hb F, Hb A2 y su cuantificación fue determinada utilizando la técnica de cromatografía líquida de alta presión, de intercambio catió (mas) nico (HPLC-CE). El ADN genómico fue aislado a partir de leucocitos de sangre periférica mediante el método de salting-out. La detección de la mutación beta talasémica fue realizada por medio de las técnicas de reacción en cadena de la polimerasa (PCR) seguida de Reverse Dot Blot. Sus parámetros hematológicos fueron: Hb: 7,0 g/dL, Hcto: 24,8%, VCM: 87,4 fl, CHCM: 27,8 fl. Los resultados de la HPLC-CE mostraron un elevado incremento en los niveles de Hb Fetal en un 97% y niveles de Hb A2 dentro de los valores normales. El estudio molecular y familiar demostró la presencia de la mutación βIVSII-849 en trans con una deleción δβ talasemia. El propósito heredó de la madre la mutación δβ-talasemia y del padre la mutación βIVSII-849. Esta es la primera vez que se ha realizado este diagnostico en una familia Venezolana, con riesgo de un heterocigoto compuesto para β-talasemia y δβ-talasemia Resumen en inglés The propositus is a two year old child with a severe hemolytic anemia and increased level of Hb F. The Hbs A, A2 and F were eluted and quantitated by cation exchange high-performance liquid chromatography (HPLC-CE). DNA was isolated from peripheral blood leukocytes by a salting-out extraction procedure. The β globin gene was amplified and the presence of the β thalassemia mutation was determined by PCR followed of Reverse Dot Blot. Her hematological parameters w (mas) ere as follows: Hb: 7.0 g/dL, Hct: 24.8%, VCM: 87.4 fl, CHCM: 27.8 fl. The haemoglobin study showed an 97% increase of Hb F and Hb A2 normal. The molecular study suggested the presence of βIVSII-849 mutation in trans to δβ Thalassemia. The propositus inherited her mother’s δβ-thalassemia gene mutation and her father’s βIVSII-849 mutation. This is the first time the diagnosis has been performed in a Venezuelan family at-risk of compound heterozygotes for β-thalassemia and delta β-thalassemia

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2

La mutacion H63D del gen HFE se asocia con un riesgo aumentado de carcinoma hepatocelular/ The H63D mutation of the HFE gene is related to the risk of hepatocellular carcinoma

Ropero, P.; Briceño, O.; López Alonso, G.; G.-Agúndez, J. A.; González Fernández, F. A.; García Hoz, F.; Villegas Martínez, A.; Díaz-Rubio, M.; Ladero, J. M.
2007-07-01

Resumen en español Objetivo: comprobar si las mutaciones del gen HFE, que pueden inducir sobrecarga hepática de hierro, guardan relación con el riesgo de desarrollar carcinoma hepatocelular (CHC) en sujetos predispuestos a sufrir este tumor. Material y métodos: se han incluido 196 pacientes (161 varones) diagnosticados de CHC. Ninguno estaba diagnosticado de hemocromatosis. El grupo control estaba constituido por 181 sujetos sanos. Todos los sujetos eran españoles de raza blanca.Las mut (mas) aciones C282Y y H63D del gen HFE se identificaron mediante reacción en cadena de polimerasa (PCR) sobre ADN genómico leucocitario utilizando enzimas de restricción específicas. Resultados (casos/controles): 1. Distribución genotípica: a) mutación C282Y: 1/0 homocigotos, 12/23 heterocigotos, 183/158 normales (p = 0,07, n.s.); y b) mutación H63D: 9/5 homocigotos, 85/52 heterocigotos, 102/124 normales (odds ratio 2,00, IC95% 1,29-3,12, p = 0,002). Cuatro casos y seis controles eran heterocigotos compuestos. 2. Frecuencias alélicas: a) mutación C282Y: normales 378/339, mutados 14/23 (p = 0,11, n.s.); b) mutación H63D: normales 289/300; mutados 103/62 (odds ratio 1,72, IC95% 1,19-2,50, p = 0,004). No se observaron diferencias en relación con el sexo, la edad o la etiología (VHC, VHB, etílica o mixta) de la hepatopatía previa. Conclusiones: la mutación C282Y no guarda relación con el riesgo de desarrollar CHC en sujetos sin hemocromatosis conocida. La posesión de la mutación H63D se asocia con un riesgo aumentado de desarrollar CHC independientemente de la etiología de la hepatopatía crónica subyacente. Resumen en inglés Aim: to disclose whether mutations in the HFE gene inducing liver iron overload are related to the risk of hepatocellular carcinoma (HCC) in otherwise predisposed patients. Patients and methods: one hundred and ninety-six patients (161 males) diagnosed with HCC and 181 healthy controls were included in the study. All subjects were white Spaniards. C282Y and H63D mutations in the HFE gene were identified in leucocyte genomic DNA using a polymerase chain reaction (PCR) and (mas) specific restriction enzymes. Results (cases/controls): 1. Genotype distribution: a) C282Y mutation: homozygotes 1/0, heterozygotes 12/23, wild type 183/158 (p = 0.07, non significant); b) H63D mutation: homozygotes 9/5, heterozygotes 85/52, wild type 102/124 (0dds ratio 2.00, 95% C.I. 1.29-3.12, p = 0.002. Four cases and 6 controls were carriers of heterozygous mixed genotypes. 2. Allele frequencies: a) C282Y mutation: wild type allele 378/339, mutated allele 14/23 (p = 0.11, non significant); b) H63D mutation: wild type allele 289/300, mutated allele 103/62 (0dds ratio 1.72, 95% C.I. 1.19-2.50, p = 0.004). Age at diagnosis, gender and etiology of the underlying liver disease do not influence these findings. Conclusion: the C282Y mutation in the HFE gene is not related to the risk of HCC in non-hemochromatosis patients. The H63D mutation is associated with a higher risk of HCC in cirrhotic patients irrespective of their underlying liver disease.

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3

Diversidad genética de piracanjuba usada en programas de repoblación con marcadores microsatélites/ Genetic diversity of piracanjuba used in stock enhancement programs with microsatellite markers

Rodriguez-Rodriguez, Maria del Pilar; Lopera-Barrero, Nelson Mauricio; Ribeiro, Ricardo Pereira; Povh, Jayme Aparecido; Vargas, Lauro; Sirol, Rodolfo Nardez; Jacometo, Carolina Bespalhok
2010-01-01

Resumen en español El objetivo de este trabajo fue estimar la diversidad genética de un lote de Brycon orbignyanus usado en programas de repoblación, a través de marcadores microsatélites. Se analizaron muestras de 44 reproductores, de 70 larvas y de 69 alevinos, con la amplificación de cinco loci descritos para Brycon opalinus. El número de alelos, la heterozigosidad observada (Ho) y esperada (He), el índice de Shannon (IS), la diversidad genética de Nei (DGN), el coeficiente de en (mas) dogamia (Fis), la distancia (DG) e identidad genética (IG), el número efectivo de alelos, el test del equilibrio de Hardy-Weinberg (EHW) y el desequilibrio de ligación fueron calculados. Reproductores y progenie tuvieron un número similar de alelos en los loci evaluados. La Ho media, IS, DGN, DG e IG mostraron que existe menor distancia genética entre parentales y larvas y una disminución de variabilidad genética en los alevinos. Fueron observados desvíos en EHW y desequilibrio de ligación en seis pares de loci. El Fis mostró exceso de heterocigotos en parentales y larvas y déficit de heterocigotos en los alevinos. El lote de reproductores está en proceso de pérdida de alelos y hubo disminución de la variabilidad genética entre la fase de larva y alevino. Resumen en inglés The objective of this work was to estimate the genetic diversity of a Brycon orbignyanus lot used in stock enhancement programs, using microsatellite markers. Samples of 44 broodstocks, 70 larvae and 69 fingerlings, were analyzed with amplification of five loci described for Brycon opalinus. The number of alleles, the observed (Ho) and expected (He) heterozygosity, Shannon index (IS), Nei's genetic diversity (DGN), the inbreeding coefficient (Fis), distance (DG) and genet (mas) ic identity (IG), the effective number of alleles, the test of Hardy-Weinberg equilibrium (EHW) and the linkage disequilibrium were calculated. Broodstocks and offspring had a similar number of alleles at the tested loci. Ho average, IS, DGN, DG and IG showed that there is less genetic distance between parental and larvae and a decrease of genetic variability in the fingerlings. Deviations in the EHW and disequilibrium ligation were observed in six pairs of loci. Inbreeding coefficient showed excess of heterozygotes in parental and larvae and heterozygote deficiencies in fingerlings. The broodstock is in process of allele losses and the genetic variability decreased between larva and fingerling stages.

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4

Frecuencia de la mutación F508del en estudiantes de la Facultad de Medicina de la Universidad del Rosario, Bogotá, Colombia/ Carrier frequency of F508del mutation of cystic fibrosis in medical students from Universidad del Rosario, Bogotá, Colombia

Mateus, Heidi Eliana; Fonseca, Dora Janeth; Sánchez, Lina S.; Peñaloza, Iván F.; Forero, Diana V.; Perdomo, Pamela A.; Quiasua, Diana C.; Ramírez, Alexander; Montoya, Laura C.; Pérez, Luis A.; Amado, Hilda P.; Molano, Jorge A.; Amaya, Sergio A.; Durán, María H.; Cárdenas, Vanesa C.; Guevara, Karen; Parga, Diego A.; Esparrogosa, Claudia L.
2007-12-01

Resumen en español Introducción: La fibrosis quística es la enfermedad letal autosómica recesiva más frecuente en caucásicos, donde su incidencia es de 1 en 2000 nacidos vivos. Se debe a mutaciones en el gen CFTR, de las cuales la más frecuente es la F508del presente en 66% de los enfermos y en 1 de cada 25 personas sanas de origen caucásico. Objetivo: Identificar la tasa de portadores de la mutación F508del en una muestra de estudiantes de la Facultad de Medicina de la Universidad (mas) del Rosario. Materiales y métodos: Se determinó la presencia de la mutación F508del mediante PCR y análisis de heterodúplex en 110 estudiantes de IV y VII semestre de la Facultad de Medicina. Resultados: Se obtuvieron 4 heterocigotos para la mutación F508del, es decir, una frecuencia de portadores de 1 en 27 estudiantes. Conclusiones: La frecuencia de portadores de esta mutación en la población analizada es considerable, e indica que hay un alto número de personas en riesgo de heredar la enfermedad y que deben recibir asesoramiento genético. Es necesario aumentar el tamaño de la muestra para obtener datos representativos de la población colombiana. Resumen en inglés Introduction: Cystic fibrosis (CF) is the most frequent autosomical recessive disorder in Caucasian population with an incidence of 1 in 2000 newborns. The disease is caused by mutations in the cftr gene, but the most common mutation is F508del, which accounts for 66% of CF chromosomes worldwide and a carrier frequency for Caucasian population of 1 in 25. Objective: To determine the carrier frequency of the F508del mutation in 110 unrelated, healthy students from the Facu (mas) ltad de Medicina, Universidad del Rosario. Methods: The presence of F508del mutation using PCR and heteroduplex analysis was determined. Results: Only four heterozygotes for F508del mutation were discovered. This represents a carrier frequency of 1 in 27 students. Conclusions: This estimated frequency of F508del carriers is higher than expected, encouraging further screening in normal control individuals from different regions of Colombia.

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5

PCR-heterodúplex por agrupamiento: Implementación de un método de identificación de portadores de la mutación más común causal de fibrosis quística en Colombia/ PCR-heteroduplex by grouping: Rapid screening carrier method for cystic fibrosis F508del mutation in Colombia

Jay, Lina Manuela; Mateus, Heidi; Fonseca, Dora; Restrepo, Carlos Martín; Keyeux, Genoveva
2006-09-01

Resumen en español Introducción: La fibrosis quística (FQ) es una enfermedad autosómica recesiva frecuente, con una incidencia de 1 en 2,500 recién nacidos. La causan más de 1,300 mutaciones distintas en el gen regulador de la conductancia transmembranal de la fibrosis quística (CFTR). Sin embargo, la mutación F508del es la más común en la mayoría de las poblaciones. Objetivos: Desarrollo de una técnica rápida, de bajo costo y confiable que permita filtrar con rapidez a los port (mas) adores o afectados por esta mutación que mediante el asesoramiento genético, contribuya a disminuir la aparición de nuevos casos y a un diagnóstico temprano de los enfermos y así lograr un descenso en la morbilidad y la mortalidad asociadas con la fibrosis quística en Colombia. Metodología: En el presente estudio se aplicó la técnica PCR-heterodúplex por agrupamientos, gracias al análisis de 400 muestras de sangre en papel filtro obtenidas de individuos asintomáticos para la FQ. Resultados: En las pruebas de validación de la técnica PCR-heterodúplex por agrupamiento se obtuvo una eficiencia, reproducibilidad y especificidad de 100% y una sensibilidad de 92%. Conclusiones: Se demostró la sensibilidad y reproducibilidad de la técnica PCR Directa-heterodúplex por agrupamientos de hasta 10 muestras, que se pueden emplear en programas para filtrar heterocigotos y afectados de F508del. Resumen en inglés Background: Cystic fibrosis (CF) is the most frequent autosomal recessive disorder in the Caucasian population with an incidence of 1 in 2,500 newborns. More than 1,300 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that causes CF have been described. However, mutation F508del is the most common mutation in different populations around the world. Objective: To develop a fast, reliable and low-cost technique to screen carriers and affected (mas) individuals for the F508del mutation. This kind of analysis will have an impact on genetic counselling to decrease the incidence of new cases, in the early diagnosis and instauration of appropriate treatment to decrease morbidity and mortality associated to CF in Colombia. Methods: The reliability of the PCR-heteroduplex by grouping technique by analysis of 400 blood spot samples from asymptomatic CF patients was defined. Results: Using PCR-heteroduplex by grouping technique 100% efficiency, reproducibility and specificity and 92%sensitivity were found. Conclusions: The sensitivity and reproducibility of the PCR-heteroduplex by grouping technique up to pooling of 10 samples were demonstrated. This kind of analysis could be used in heterozygotes and affected screening programs.

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6

Manejo renal de la ß2 microglobulina: Su significado en portadores de la nefronoptisis del adolescente/ Renal handling of ß2 microglobulin: Its significance in carriers of adolescent nephronophthisis (NPH3)

Fernández, Carmen; Araque, Carolina; Méndez, Jorge; Angulo, Luisa; Fargier, Bernardo
2007-06-01

Resumen en español La nefronoptisis del adolescente (NPH3) constituye una variedad de la nefronoptisis. En Venezuela, la incidencia anual está alrededor de 1 a 3 casos por año y todos los casos pertenecen a un árbol genealógico común. El presente estudio tuvo como objetivo evaluar la función tubular proximal en pacientes portadores del gen de la NPH3 con función renal conservada, para lo cual se utilizó como marcador biológico la ß2 microglobulina (ß2M). Se incluyeron en el estud (mas) io 8 pacientes: 7 portadores heterocigotos y un homocigoto del gen de la NPH3 y 10 controles sanos. Se determinaron las concentraciones plasmáticas y urinarias de ß2M y se calcularon los índices de ß2M urinaria/creatinina urinaria, así como la excreción fraccional de ß2M, la ß2M filtrada y el porcentaje de reabsorción de ß2M. Se evidenció un aumento de la concentración plasmática de ß2M no relacionada con disminución de la filtración glomerular. La excreción urinaria de ß2M así como los índices urinarios relación U ß2M /UCr y la excreción fraccionada de ß2M fueron normales. La carga filtrada estuvo elevada sin aumento en la excreción con un porcentaje de reabsorción normal. En el grupo estudiado no se demostró una alteración en la excreción urinaria de ß2M; se evidenció un aumento en la carga filtrada sin aumento en el porcentaje de reabsorción ni en la excreción lo que plantea otro mecanismo de captación o de degradación de la sustancia a nivel del tubulo contorneado proximal, mecanismo aún no dilucidado. Resumen en inglés The adolescent nephronophthisis (NPH3) is a variant of the nephronophthisis. In Venezuela, one to three patients have been registered each year, all of them belonging to the same family tree. The objective of this study was to evaluate the function of the proximal convoluted tubule in NPHP3 carriers; using the ß2M as biological marker. Eight carriers, 7 heterozygotes and l homozygote, with normal renal function were compared with a 10 healthy subjects (control group). Se (mas) rum ß2 microglobulin (ß2M), urinary ß2M, the quocient urinary ß2M/urinary creatinine and the ß2M fractional excretion were determinated. The filtered ß2M and the percentage of reabsortion were calculated. We observed an increase in the plasmatic concentration of ß2M but not related with a decrease of the glomerular filtration. The urinary ß2M, the ß2M/urinary creatinine relation and the fractional excretion of ß2M were normal. The filtered load of ß2M was elevated without increase in the excretion or percentage of reabsortion. We conclude that in our group of NPH3 carriers, functional changes in the proximal convoluted tubule, when measured by urinary excretion of ß2M, were absent. This finding suggests the existence of other mechanism of uptake or degradation of the substance in the proximal convoluted tubule, which have yet to be elucidated.

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7

Distribución del polimorfismo del codón 72 del gen p53 en lesiones de cuello uterino

Cruz Gómez, Jhon Fredy; Quintero Vega, Militza; Fernández, Liliana; Condezo, Gabriela; Bastidas, Marco; Puig Pons, Juan
2010-03-01

Resumen en español Objetivo: Determinar la distribución del polimorfismo del codón 72 del gen p53 en pacientes que presentan lesiones cervicales asociadas a infección por VPH. Métodos: Estudio descriptivo de corte transversal donde se procesaron 118 muestras del área genital femenina, de 59 mujeres sanas (controles) y 59 con lesiones cervicales NICI-NICII-NICIII y Ca in situ (casos), para la extracción y purificación del ADN. Se amplificó el exón 4 del gen p53, para la genotipifica (mas) ción del codón 72 mediante la técnica PCR-SSCP. Ambiente: Facultad de Ciencias, Laboratorio de Biología y Medicina Experimental LABIOMEX, Universidad de Los Andes. Mérida, Estado Mérida, Venezuela. Resultados: La PCR-SSCP permitió determinar la frecuencia de los genotipos homocigotos arginina (Arg/Arg), prolina (Pro/Pro) y heterocigoto prolina/arginina (Pro/Arg). Para los casos el genotipo Arg/Arg tuvo una frecuencia de 32,20 % y para los controles de 50,85 %. El genotipo Pro/Pro se encontró en 5,09 % de los casos y 11,86 % para los controles. El genotipo Pro/Arg tuvo una distribución de 62,71 % para los casos y 37,29 % para los controles. Conclusión: En este estudio no se encontró una relación estadísticamente significativa entre la presencia del genotipo Arg/Arg y el desarrollo de lesiones cervicales. Resumen en inglés Objective: To determine the distribution of the polymorphism of the codon 72 of the gene p53 in patients that present cervical lesions associated to infection by VPH. Method: Descriptive and transversal study through assessment of 118 samples of the genital feminine area were processed, of 59 healthy (control) women and 59 with cervical lesions NICI-NICII-NICIII and Ca in situ (cases), for the extraction and purification of the DNA. The exon 4 of the gene p53 was amplifie (mas) d, for the genotipification of the codon 72 by means of technical PCR-SSCP. Setting: Facultad de Ciencias, Laboratorio de Biologia y Medicina Experimental LABIOMEX, Universidad de Los Andes. Merida, Estado Merida, Venezuela. Results: PCR-SSCP allowed determining the frequency of the homozygotes genotypes arginine (Arg/Arg), proline (Pro/Pro) and heterozygotes proline /arginine (Pro/Arg). For the cases the genotype Arg / Arg had a frequency of 32.20 % and for the controls of 50.85 %. The genotype Pro/Pro was in 5.09 % of the cases and 11.86 % for the controls. The genotype Pro/Arg had a distribution of 62.71 % for the cases and 37.29 % for the controls. Conclusion: In this investigation there was not a statistically significant relationship among the presence of the genotype Arg/Arg and the development of cervical lesions.

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Ética científica de la terapia génica de individuos: Urgencia de la Cirugía Génica del ADN/ Scientific ethics of gene therapy for individuals: The urgency for DNA gene surgery

Valenzuela, Carlos Y
2003-10-01

Resumen en inglés Gene therapy for individuals is mainly directed to somatic or germ cells. The present technology aims to insert a DNA segment in the recipient cells. This therapy is useful in Mendelian recessive diseases. There is an ethical moratorium to perform insertion gene therapy in germ cells, because this procedure increases the human genome. Somatic cell gene therapy cures individuals but increases the gene frequency of genetic diseases in the population. This occurs because the (mas) descendants of the cured patient should carry his or her «ill» genes. We denote by «DNA gene surgery» the procedure that replaces «ill» nucleotide(s) by healthy one(s) conserving the genome size and the gene context of expression and regulation. Several procedures for gene surgery have been applied to cells and animals. Those based on DNA repair as Chimeric RNA/DNA, one stranded oligonucleotides and tristranded DNA. Those based on DNA recombination with oligo-DNA or one stranded DNA, and transposable DNA segments. Gene surgery can be applied to germ cell gene therapy without ethical contraindications. It can cure Mendelian dominant diseases and it can be applied to heterozygotes. It preserves the regulation and expression gene context. If a technical safe procedure is available, the entire mankind could be treated and cured of all the Mendelian diseases, in one generation. Susceptibilities for all diseases could also be treated. The moratorium for research on germ cell gene therapy by gene surgery should be interrupted. Safe gene surgery is a moral imperative for gene therapy of patients and their descendants, for the treatment of dominant genetic diseases and for heterozygous carriers of recessive disorders (Rev Méd Chile 2003; 131: 1208-14)

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Variación isoenzimática de Pinus hartwegii Lindl. en un gradiente altitudinal en Michoacán, México/ Isoenzymatic variation of Pinus hartwegii Lindl. along an altitudinal gradient in Michoacan, Mexico

Viveros-Viveros, Héctor; Tapia-Olivares, Blanca L.; Sáenz-Romero, Cuauhtémoc; Vargas-Hernández, J. Jesús; López-Upton, Javier; Santacruz-Varela, Amalio; Ramírez-Valverde, Gustavo
2010-09-01

Resumen en español Para conocer la variación genética en un gradiente altitudinal y generar lineamientos para la conservación de Pinus hartwegii Lindl., se investigó la variación genética isoenzimática entre poblaciones de esta especie a diferentes altitudes en el Parque Nacional Pico de Tancítaro, Michoacán, México. Se recolectaron semillas de cuatro localidades ubicadas a 3000, 3200, 3400 y 3600 m de altitud. Se encontró polimorfismo en 11 de los 12 loci examinados. La heteroci (mas) gosidad esperada promedio (He) fue 0.12. En tres loci existió desequilibrio de Hardy-Weinberg (p Resumen en inglés To determine the genetic variation along an altitudinal gradient and generate guidelines for the conservation of Pinus hartwegii Lindl., genetic isoenzymatic variation was studied in populations of the species at different altitudes in Pico de Tancítaro National Park, Michoacán, México. Seeds were collected from four locations at altitudes of 3000, 3200, 3400 and 3600 m. Polymorphism was found in 11 of the 12 loci examined. The expected average heterozygosity (He) was (mas) 0.12. At three loci there was Hardy-Weinberg non equilibrium (p

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Síndrome de exceso aparente de mineralocorticoides por déficit de 11 ß hidroxiesteroide deshidrogenasa.: Estudios clínicos y genéticos en una familia chilena afectada seguida por 19 años/ A syndrome of apparent mineralocorticoid excess associated with a deficiency of 11ß-hydroxysteroid dehydrogenase

Rodríguez P, José Adolfo
2000-01-01

Resumen en inglés An 11-year old girl was seen in 1981 with hypokalemia, low renin, low aldosterone, and severe hypertension. A medical adrenalectomy with dexamethasone and aminoglutethimide, and the blockade of mineralocorticoid receptors with spironolactone improved her condition, but the blockade of glucocorticoid receptors with RU-486 worsened it. An aldosterone infusion induced no changes. A sister was born in 1982 with similar findings. Both patients had an impaired ability to conver (mas) t cortisol to cortisone after an oral load of 200 mg cortisol. In urine, an elevated ratio for metabolites of cortisol to metabolites of cortisone was found. These data suggested a defect in the activity of renal 11ß-hydroxysteroid dehydrogenase. Both parents were asymptomatic, phenotypically normal and non-consanguineous. Their urinary metabolites of cortisol and cortisone were normal before and after stimulation with ACTH. However, the mother reached a peak plasma cortisone concentration 3 SD below the mean reached by normal subjects after an oral 200-mg cortisol load, a fact that suggests that this test could be used to detect heterozygotes. The genetic studies revealed a homozygous mutation on exon 3 of the HSD11K gene, which by substituting TGC for CGC changes Arg 213 for Cys and induces a loss of 84% of the enzymatic activity in transfected cells. Both unrelated parents had the same heterozygous mutation. Both patients have been treated with dexamethasone but have also required spironolactone. The older sister has also required high doses of nifedipine to lower her blood pressure. After 19 years of follow-up, the older sister has become normotensive and normokalemic under therapy, and reached a final height of 140 cm at age 17. The younger sister has increased her mean blood pressure at a rate of 1 mm Hg per year, in spite of treatment. Her final height is 143.5 cm. (Rev Méd Chile 2000; 128: 17-26)

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Frecuencias alélicas, genotípicas y haplotípicas HLA-A, HLA-B, HLA-DRB1 en donantes fallecidos, Medellín, Colombia/ Human leucocyte antigen gene (HLA-A, HLA-B, HLA-DRB1) frequencies in deceased organ donors

Rodríguez, Libia M; Giraldo, Mabel C; García, Natalia; Velásquez, Laura; París, Sara C; Álvarez, Cristiam M; García, Luis F
2007-12-01

Resumen en español Introducción. La caracterización genética del sistema HLA es de gran utilidad en estudios antropogenéticos, en la comprensión de mecanismos asociados a susceptibilidad o resistencia a diversas enfermedades, en los fenómenos inmunológicos durante el embarazo y en la selección de donantes/receptores en trasplantes de órganos. Objetivo. Determinar las frecuencias alélicas, genotípicas y haplotípicas HLA-A, -B, -DRB1 en donantes fallecidos en Medellín. Materiales (mas) y métodos. Se incluyeron 926 donantes entre febrero de 1989 y septiembre de 2006, a los cuales se les realizó la tipificación HLA-A, -B, -DRB1 por PCR-SSP (single specific primer-polymerase chain reaction) de mediana resolución. Las frecuencias alélicas, genotípicas y haplotípicas fueron estimadas mediante el algoritmo de máxima verosimilitud. Se evaluó el ajuste al equilibrio de Hardy-Weimberg por una prueba exacta análoga a la de Fisher usando la cadena de Markov, así como el desequilibrio de ligamiento entre pares de loci. Resultados. Se identificaron 22, 43 y 14 alelos para los loci HLA-A, -B, -DRB, respectivamente, de los cuales los más frecuentes fueron: A*02, A*24, B*35 y DRB1*04. En los loci HLA-A y -B se observó deficiencia en la frecuencia de heterocigóticos esperada (p Resumen en inglés Introduction. Genetic characterization of the human leucocyte antigen (HLA) system has provided insights into mechanisms of susceptibility to diverse diseases and immunological phenomena during pregnancy, as well as providing evidence for compatibility in the selection of organ transplant donors and recipients. Objective. The HLA-A,-B,-DRB1 allele, genotype and haplotype frequencies were determined in deceased organ donors in Medellín, Colombia. Materials and methods. Th (mas) e genotypes of 926 deceased donors were evaluated over a 17-year period (1989- 2006). HLA-A, HLA-B and HLA-DRB1 typing was performed by sequence specific primer-polymerase chain reaction (SSP-PCR). Maximum likelihood frequencies were estimated by the zipper version of expectation maximation algorithm. Hardy-Weinberg equilibrium were determined by an exact test analogous to Fisher’s test by using Markov’s chain, and linkage disequilibrium between pairs of loci. Results. Twenty-two, 43 and 14 alleles were identified for HLA-A, -B and -DRB loci, respectively. The most frequent were A*02, A*24, B*35, and DRB1*04. A deficiency in the proportion of heterozygotes in HLA-A and B loci (p

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Forma familiar de la enfermedad de Creutzfeldt-Jakob: marcadores genéticos en 4 familias chilenas/ Genetic markers in four Chilean families with familial Creutzfeldt-Jakob disease

Cartier R, Luis; Fernández O, Jorge; Ramírez V, Eugenio
2006-09-01

Resumen en inglés Background: Creutzfeldt-Jakob disease (CJD) is a form of transmissible spongiform encephalopathy, in which a prion protein (PrP Sc) accumulates in the brain of affected individuals. Chile has a prevalence of CJD that is more than twice than in the rest of the world and has the highest rate of familial forms. These later forms are associated with the heterozygocity of codon 200 of PrP protein gene. Aim: To search susceptibility genetic markers of CJD in members of families (mas) affected by CJD. Material and methods: A blood sample was obtained from 50 individuals pertaining to four families affected by CJD. DNA from peripheral mononuclear cells was amplified by polymerase chain reaction and sequenced for the gene that codifies PrP protein. Results: In family A, 21 of 23 members were homozygotes for codon 129 (Met/Met) and eight were simultaneously heterozygotes for codon 200 (Glu/Lys). In family B, six of nine members were homozygotes for codon 129, five were heterozygotes for codon 200 and four had both mutations. In family C, the four analyzed subjects were homozygotes for codon 129 and two were simultaneously heterozygotes for codon 200. In family D, nine of 14 members were homozygotes for codon 129 and two were simultaneously homozygotes for codon 200. No family had polymorphisms for codon 219. Conclusions: Thirty two percent of analyzed subjects were homozygotes for codon 129 and heterozygotes for codon 200, condition that defines the genetic susceptibility to acquire CJD. The dominant tendency of these genotypes could explain the higher incidence of CJF in Chile

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Fibrosis quística: diagnóstico molecular en 93 pacientes argentinos y detección familiar de portadores. Impacto asistencial y proyección a nuevos avances terapéuticos/ Molecular diagnosis of cystic fibrosis in 93 argentinean patients and detection of heterozygotes in affected families: Impact on health services and therapeutic advances

Oller de Ramírez, Ana M; Ghio, Addy; Melano de Botelli, Myrna; Dodelson de Kremer, Raquel
2008-08-01

Resumen en español Introducción. La fibrosis quística es una enfermedad autosómica recesiva causada por más de 1.500 mutaciones y variantes en el gen regulador de la conductancia transmembrana. Objetivos. Establecer el espectro y frecuencia de mutaciones en este gen en pacientes argentinos. Detectar portadores en las familias involucradas. Material y métodos. Se investigó en 91 pacientes, clínica y bioquímicamente confirmados con 2 pruebas de sudor positivas y en 2 adultos estérile (mas) s. Se trabajó con 165 familiares. El diagnóstico molecular comprendió 3 etapas consecutivas: a) determinación de 29 mutaciones frecuentes; b) haplotipos por microsatélites; c) pesquisa completa del gen por análisis conformacional de hebra simple y electroforesis en gel de gradiente desnaturalizante con secuenciamiento de los patrones anormales. Determinado el genotipo de los pacientes, se investigó el estado de portador en los familiares. Resultados.1er Objetivo: Se identificaron 14 mutaciones, se detectaron otras 3 mutaciones y se caracterizaron otras 11 mutaciones, tres de ellas nuevas (p.G27R, c.622-2A>G, p.W277R). En total, se identificaron 28 mutaciones responsables del 90,3% de los alelos mutados, 14 con una frecuencia superior al 1%. 2º Objetivo: De 165 personas investigadas, 143 fueron portadores y 22 con genotipo normal. Conclusiones. Este trabajo contribuyó a la caracterización molecular de pacientes con fenotipos clásicos y atípicos y a la detección de numerosos portadores. Las investigaciones fármaco-terapéuticas recientes se basan en el tipo de mutación. Por lo tanto, conocer las mutaciones de los pacientes (genotipo) tiene significativa importancia para la futura aplicación de terapias específicas. Resumen en inglés Introduction. The cystic fibrosis is an autosomal recessive disease caused by more than 1500 mutations and variants in the cystic fibrosis transmembrane conductance regulator gene. Objectives. To establish the spectrum and frequency of mutations on this gene in Argentinean patients.To detect heterozygotes in affected families. Patients and methods. We investigated 91 clinical and biochemically confirmed patients with 2 elevated sweat tests and 2 sterile adults. We worked (mas) with 165 relatives. The molecular diagnosis was accomplished in 3 serial stages: a) determination of 29 frequent mutations; b) haplotypes for microsatellites; c) an extensive screening of gene through single strand conformation analysis and multiplex denaturing gradient gel electrophoresis with sequencing of abnormal patterns. Once patient's genotype was confirmed, we investigated the heterozygotes' state in the relatives. Results. 1st Objective: Fourteen mutations were identified. Three more mutations were detected and other 11 mutations were characterized, 3 of them novel (p.G27R, c.622-2A>G, p.W277R). In total, we have identified 28 mutations responsible for 90.3% of the mutated alleles, 14 with a higher frequency than 1%. 2ndObjective: From 165 investigated people, 143 were confirmed as heterozygotes and with normal genotype 22. Conclusions. This work contributed to the molecular characterization of patients with classic and atypical phenotypes and to the detection of great numbers of carriers. New pharmacological therapeutic investigations are based on the mutation type. Therefore, knowledge of patients, mutations (genotype) has significant importance for the future application of specific therapies.

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Estudio de tres loci hipervariables en población mixta chilena/ Study of three hypervariable loci in a mixed Chilean population

Novoa C, M del Rosario; Labbé C, Carolina; Jorquera G, Hugo; Moreno Ch, Fabián; Aguirre M, M Eugenia; Cifuentes O, Lucía
2001-01-01

Resumen en inglés Background: Genetic markers are useful to study evolution parameters in populations and to determine kinship. Aim: To characterize three short tandem repeat loci in a sample of Chilean subjects and compare them with Caucasian and Hispanic populations. Material and methods: Three hundred ninety three unrelated subjects that were sent for genetic studies from courts of justice, were studied. The loci FESFPS, F13A01 and vWA in blood samples, were typified amplifying DNA by p (mas) olymerase chain reactions. Results: The three studied loci were highly polymorphic. F13A01 and FESFPS were in Hardy-Weinberg genetic equilibrium. A significant excess of heterozygotes was detected for vWA locus. There were no differences in allele frequencies, according to ethnic origins of last names. Allele frequencies for F13A01 and vWA loci were similar to those of Hispanic populations of Unites States and FESFPS loci was different. Conclusions: All three loci had a high efficiency for genetic identification tests according to the estimated a priory exclusion probability (Rev Méd Chile 2001; 129: 75-79)

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Combinación de genotipos DRD4 y DAT1 constituye importante factor de riesgo en miembros de familias de Santiago de Chile con déficit atencional/ Combination of DRD4 and DAT1 genotypes is an important risk factor for attention déficit disorder with hyperactivity families living in Santiago, Chile

Henríquez B, Hugo; Henríquez H, Marcela; Carrasco Ch, Ximena; Rothhammer A, Paula; Llop R, Elena; Aboitiz, Francisco; Rothhammer E, Francisco
2008-06-01

Resumen en inglés Background: Attention deficit/hyperactivity disorder (ADHD) is a common, highly heritable neurobiological disorder of childhood onset, characterized by hyperactivity, impulsiveness, and/or inattentiveness. Aún: To search forpossible associations between dopamine receptor D4 (DRD4) and dopamine transponer 1 (DATl) polymorphisms and ADHD in Chilean families. Material and methods: We extended a previous family-based discordant sib pair analysis that included 26 cases diagno (mas) sed according to DSM-IV entena and 25 controls (healthy siblings of cases), adding 14 cases and 11 controls. Results: Both loci, individually classified as homozygotes or heterozygotes for the DRD4 7-repeat and DATl 10-repeat alleles, did not exhibit genotype frequency differences between affected children and their healthy siblings. However, the simultaneous presence of both DRD4 7-repeat heterozygosity and DATl 10 allele homozygosity was significantly higher (22.5%) in cases (40), compared with (2.8%) unaffected siblings (36), with an odds-ratio of 10.16. Conclusions: The genotype combination DRD4/7 heterozygotes and DAT1/10 homozygotes is a high risk factors in Chilean families for ADHD. Increased density of dopamine transporters in ADHD brains, along with abundance of 7-repeat D4 receptors in prefrontal cortex, which is impaired in ADHD patients, make the observed gene-gene interaction worthy of studies to understand the functional basis ofADHD

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Análisis de diversidad genética en tres poblaciones de llamas (Lama glama) del noroeste argentino/ Analisis of genetic diversity in three llama (Lama glama) populations from north-western Argentina

BUSTAMANTE, ANA V; MATÉ, MARÍA L; LAMAS, HUGO E; GIOVAMBATTISTA, GUILLERMO; ZAMBELLI, ANDRÉS; VIDAL-RIOJA, LIDIA
2006-06-01

Resumen en español Este trabajo describe la variabilidad genética actual de tres poblaciones de llamas (Lama glama) del noroeste argentino (NOA), afectadas a la producción de fibra. Originariamente, las tropas fueron una única población la cual fue subdividida hace 10 años. Se estudiaron muestras de ADN de 77 animales mediante amplificación por PCR de 12 loci microsatélite con cebadores específicos de llama. La alta variabilidad genética comprobada se sustenta en el hallazgo total (mas) de 140 alelos diferentes, 9 a 16 alelos por locus y rangos de heterocigosidad observada y esperada por locus de 1 a 0 y 0,9 a 0,47, respectivamente. Diecinueve de treinta y seis pruebas de equilibrio de Hardy-Weinberg mostraron desvíos significativos (P Resumen en inglés The current genetic variability of three llama (Lama glama) management units from the northwestern Argentine (NOA) was analyzed. The troops, originally comprised a unique population that 10 years ago was divided into the current three. The DNA of 77 animals was studied by PCR amplification of 12 loci using microsatellite primers specific of Lama glama. A high level of genetic variability is sustained by the finding of one hundred and forty total alleles, a range of 9 to 1 (mas) 6 allele number per locus and observed and expected hetrozygosities per locus varying from 1 to 0 and 0.9 to 0.47, respectively. Distributed within the three troops 44 private alleles were detected and proposed for uses such as to exchange new allelic variants. Hardy Weinberg Equilibrium test for each locus within each population showed significant deviation (P

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