RESUMO
Fragile X syndrome is the most common form of inherited mental retardation in men. The molecular mechanism underlying the disease is an amplification of a polymorphic trinucleotide repeat (CGG)n located at 5' end of FMR1 which promotes transcriptional silencing of the gene. Four different classes of alleles could be distinguished in the population based on the size of the repeat, however only large amplifications over 200 CGG are associated with the disease. In the past decade several authors have associated premutated alleles, which harbor expansions from 61 to 200 repeats, with the occurrence of premature ovarian failure (POF). In this work we describe a large Brazilian family in which a POF/premutated woman has transmitted to five out of seven daughters a FMR1 premutated allele. From these five women with premutations, three have experienced premature ovarian failure. Our data clearly indicate a co-segregation pattern of inheritance between POF and fragile X premutation.
Assuntos
Segregação de Cromossomos , Cromossomos Humanos X/genética , Proteínas do Tecido Nervoso/genética , Insuficiência Ovariana Primária/genética , Proteínas de Ligação a RNA , Adulto , Alelos , Brasil , Feminino , Proteína do X Frágil da Deficiência Intelectual , Inativação Gênica , Humanos , Masculino , Linhagem , Repetições de TrinucleotídeosRESUMO
FRAXE (FMR2) is a fragile site associated with mental impairment located in Xq28, 600 kb distal to FRAXA (FMR1), the fragile X syndrome fragile site. The FRAXE mutation is an expansion of a CCG repeat that results in methylation of a nearby CpG island. FRAXE alleles could be divided into four categories: normal (6-30 CCG repeats), intermediate (31-60 CCG repeats), premutation (61-200 CCG repeats), and full mutation (over 200 repeats). We have developed a non-isotopic polymerase chain reaction (PCR)-based assay for the identification of FRAXE full mutation alleles among mentally impaired men. In this novel PCR test for the FRAXE locus, we used three primers to permit an amplification of a 223 bp monomorphic internal control fragment in addition to the amplification of a 419 bp (CCG)(16) FRAXE locus band. A linear series of 93 male patients referred for FRAXE testing but found to be negative for the (CCG)(n) expansion in the FMR2 gene by Southern blotting analysis were retested by our PCR technique. In addition, we analyzed two positive controls consisting of a FRAXE fully mutated male and one male with a Xq terminal deletion. The developed PCR test showed accuracy of 100% in the normal individuals retested by PCR analysis, as well as in the two positive control samples utilized, in which the strategy of multiplex amplification worked as expected. Although not suitable for medical diagnosis of females and mosaics, it constitutes an important strategy for PCR typing and for FRAXE population screening.
Assuntos
Síndrome do Cromossomo X Frágil/genética , Testes Genéticos/métodos , Deficiência Intelectual/genética , Mutação/genética , Proteínas Nucleares/genética , Transativadores/genética , Alelos , Southern Blotting , Ilhas de CpG/genética , Síndrome do Cromossomo X Frágil/diagnóstico , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Dados de Sequência Molecular , Mosaicismo/genética , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Expansão das Repetições de Trinucleotídeos/genéticaRESUMO
PURPOSE: Report the initial surgical experience with four cases utilizing a pulmonary autograft for aortic valve replacement. METHODS: Four patients, all males, white, age between 23 and 46 years having aortic valve disease were submitted to aortic valve replacement with a pulmonary autograft using the root replacement technique. Right ventricular outflow tracts were reconstructed with antibiotic sterilized pulmonary or aortic homografts. All patients had control bidimensional eco-doppler (ECO) and hemodynamic study to evaluate the function of the implanted auto and homografts. RESULTS: All patients had an excellent post-operative recovery, without the necessity of inotropic drugs. All presented in normal sinus rhythm. Post-operative ECO and hemodynamic studies revealed excellent function of the implanted autografts, without gradients in three and with a 15mmHg mean residual gradient in one case. There was no regurgitation in three cases and only trace aortic insufficiency in one. The right sided homografts also showed good function, with no gradient in two cases and mean systolic gradient of 6 and 8mmHg in the other two. CONCLUSION: The pulmonary autograft procedure should be implemented definitely in our country.
