Estudios de la región 5'UTR del gen FMR-1 en pacientes con falla ovárica prematura / Studies of the 5' - UTRTR region in the FMR-1 gene in patients withe Premature Ovarian Failure

La falla ovárica prematura (FOP) es un síndrome de patogénesis multicausal que afecta aproximadamente al 1% de las mujeres en edad reproductiva. Numerosos estudios asocian el estado de premutación (amplificación del número de tripletes CGG entre 50/55 y 200 repeticiones) en el gen FMR-1 y FOP. Alrededor de un 4% de las pacientes FOP presentan alelos con premutación. La amplificación del número de tripletes por encima de 200 repeticiones causa el Síndrome de Fragilidad del X (SFX). El objetivo del presente trabajo fue estudiar la región 5´ no codificante del gen en un grupo de pacientes FOP de Argentina. La región de interés se amplificó por PCR a partir de muestras de ADN de 100 pacientes FOP y 145 mujeres controles. Los alelos de las pacientes y controles fueron agrupados en 7 categorías de acuerdo al número de tripletes obtenidos. Se observó que el número de repeticiones más frecuente se encuentra en el rango de 26 a 30 tripletes, tanto en pacientes como en controles. En el grupo de pacientes FOP, 5/197 (2.6%) alelos no relacionados estudiados presentaron un número de tripletes CGG mayor a 50, mientras que sólo 1 de 290 (0.34%) para el grupo control. Todas las pacientes FOP con valores de tripletes CGG mayor a 50 presentaron amenorrea secundaria. Estos resultados están en concordancia con lo comunicado para otras poblaciones acerca de la existencia de una asociación entre la premutación del gen FMR-1 y el desarrollo de FOP. Asimismo, los resultados obtenidos refuerzan la importancia de la genotipificación del gen FMR-1 en las pacientes FOP, a los efectos de estimar el riesgo de su descendencia para el SFX.

Premature ovarian failure (POF) is a syndrome of multicausal pathogenesis that affects 1% of women before the age of 40. Several studies associate the premutation state (CGG repeats increased in number between 50/55 and 200) in the FMR-1 gene and POF. About 4% of POF women have alleles in the FMR-1 gene in the permutation range. An increase above 200 in the number of triplets in this gene causes the Fragile X Syndrome (FXS). The purpose of the present study was to analyze the 5´untranslated region of the FMR-1 gene in a group of patients from Argentina. The region of interest was amplified by PCR from DNA samples of 100 POF patients and 145 control women. Alleles from controls and patients were grouped in 7 categories according to the number of triplets obtained. We observed that the most frequent number of repeats ranged from 26 to 30 triplets, in both patient and control groups. In the POF group, 5 out of 197 (2.6%) not related alleles presented a number of CGG triplets higher than 50, while only 1 out of 290 (0.34%) was present in controls. All POF patients with a number of CGG repeats higher than 50 presented secondary amenorrhea. These results are in accordance with previous reports from other populations showing an association between the premutation state in the FMR-1 gene and POF development. In addition, these results reinforce the importance of genotyping POF patients to estimate the risk of their offspring for Fragile X Syndrome.

Polimorfismo do exon 20 do gene da elastina em indivíduos portadores de doença diverticular dos cólons / Polymorphism of 20 of elastin gene in individuals with colonic diverticular disease

A doença diverticular dos cólons (DDC) é relacionada à dieta, pressão intraluminal elevada, bem como alterações estruturais da parede intestinal. Pacientes com alterações genéticas do gene da elastina (ELN), como a estenose aórtica supravalvar e a cútis laxa, podem manifestar hérnia, diverticulose e disfunção urinária. Recentemente, uma mutação pontual no exon 20 do ELN foi demonstrada em pacientes com hérnia inguinal. No presente estudo é demonstrada uma mutação pontual (AGTGGT) no códon 422 do exon 20 do ELN em 5/14 pacientes com DDC e em 0/26 controles. Foi observada uma associação significativa desta mutação com o desenvolvimento da DDC. /Colonic diverticular disease (CDD) is related to diet, increased intraluminal pressure and structural changes within intestinal wall. Patients carrying genetic disorders of elastin (ELN) gene, such as supravalvular aortic stenosis and cutis laxa, may present hernias, diverticulosis and bladder dysfunction. Recently, a punctual mutation in exon 20 of ELN gene was detected in patients with inguinal hernia. Present study demonstrates a punctual mutation (AGTGGT) within codon 422 of ELN gene in 5/14 patients carrying CDD and in 0/26 among controls. This investigation demonstrated a significant association between the mutation found and CDD development...