Made available in DSpace on 2014-12-17T14:16:20Z (GMT). No. of bitstreams: 1 GiocondaDRL.pdf: 1031402 bytes, checksum: 0016e69e527bddffea93909fa2748a03 (MD5) Previous issue date: 2007-08-29 / Hereditary Hemochromatosis (HH) is a genetic disease caused by high iron absorption and deposition in several organs. This accumulation results in clinical disturbances such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders and skin darkening. The H63D and C282Y mutations are well defined in the hemochromatosis etiology. The aim of this paper was that of identifying the H63D and C282Y genetical mutations in the hemochromatosis gene and the frequency assessment of these mutations in the HFE protein gene in patients with hyperferritin which are sent to the DNA Center laboratory in Natal, state of Rio Grande do Norte. This paper also evaluates the HH H63D and C282Y gene mutations genotype correlation with the serum ferritin concentration, glucose, alanine aminotransferasis, aspartato aminotransferasis, gama glutamil transferasis and with the clinical complications and also the interrelation with life habits including alcoholism and iron overload. The biochemical dosages and molecule analyses are done respectively by the enzymatic method and PCR with enzymatic restriction. Out of the 183 patients investigated, 51,4% showed no mutation and 48,6% showed some type of mutation: 5,0% were C282Y heterozygous mutation; 1,1%, C282Y homozygous mutation; 31%, H63D heterozygous mutation; 8,7%, H63D homozygous mutation; and 3,3%, heterozygous for the mutation in both genes. As to gender, we observed a greater percentage of cases with molecular alteration in men in relation to women in the two evaluated mutations. The individuals with negative results showed clinical and lab signs which indicate hemochromatosis that other genes could be involved in the iron metabolism. Due to the high prevalence of hemochromatosis and taking into account that hemochromatosis is considered a public health matter, its gravity being preventable and the loss treatment toxicity, the early genetic diagnosis is indicated, especially in patients with high ferritin, and this way it avoids serious clinical manifestations and increases patients' life expectation. Our findings show the importance of doing such genetic studies in individuals suspected of hereditary hemochromatosis due to the high incidence of such a hereditary disease in our region / A hemocromatose heredit?ria (HH) ? uma doen?a gen?tica causada pela absor??o e deposi??o elevada de ferro em v?rios ?rg?os. Este ac?mulo resulta em complica??es cl?nicas como cirrose, artrite, cardiopatias, diabetes, desordens sexuais e escurecimento da pele. As muta??es H63D e C282Y est?o bem definidas na etiologia da hemocromatose. O objetivo deste trabalho foi a identifica??o das muta??es gen?ticas H63D e C282Y no gene da Hemocromatose e avalia??o da freq??ncia dessas muta??es no gene da prote?na HFE em pacientes com hiperferritinemia que s?o encaminhados ao laborat?rio DNA Center Natal / RN. Al?m disso, avaliar a correla??o dos gen?tipos das muta??es H63D e C282Y do gene da HH com a concentra??o s?rica da ferritina, glicose, alanina aminotransferase, aspartato minotransferase, gt e com as complica??es cl?nicas e ainda a interrela??o com os h?bitos de vida incluindo o etilismo e dieta com sobrecarga de ferro. As dosagens bioqu?micas e an?lises moleculares foram realizadas respectivamente atrav?s do m?todo enzim?tico e PCR com restri??o enzim?tica. Dos 183 pacientes investigados 51,4% apresentaram aus?ncia de muta??o e 48,6% com algum tipo de muta??o: 5,0% C282Y heterozigoto mutado; 1,1% C282Y homozigoto mutado; 31% H63D heterozigoto mutado; 8,7% H63D homozigoto mutado; e 3,3% heterozigoto para a muta??o em ambos os genes. Com rela??o ao sexo, observou-se o maior percentual de casos com altera??o molecular em homens em rela??o a mulheres nas duas muta??es avaliadas. Os indiv?duos com resultados negativos apresentaram sinais cl?nicos e laboratoriais indicativos de hemocromatose sugerindo que outros genes poder?o estar envolvidos no metabolismo do ferro. Devido ? alta preval?ncia da hemocromatose, e tendo em vista que a hemocromatose ? considerada um problema de sa?de p?blica, sua gravidade ser preven?vel e a baixa toxicidade do tratamento, o diagn?stico gen?tico precoce torna-se indicado, principalmente nos pacientes com ferritina elevada, e com isso evitar manifesta??es cl?nicas graves e aumentar a expectativa de vida dos pacientes com esta doen?a. Nossos achados mostram a import?ncia da realiza??o de estudos gen?ticos em indiv?duos com suspeita de hemocromatose heredit?ria em virtude de elevada incid?ncia dessa doen?a de cunho heredit?rio em nossa regi?o

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2016-01-04T19:56:38Z No. of bitstreams: 1 GiocondaDiasRodriguesLeao_TESE.pdf: 44025376 bytes, checksum: 9da025324f9108141027f1f3a1cc3e16 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2016-01-05T20:29:30Z (GMT) No. of bitstreams: 1 GiocondaDiasRodriguesLeao_TESE.pdf: 44025376 bytes, checksum: 9da025324f9108141027f1f3a1cc3e16 (MD5) / Made available in DSpace on 2016-01-05T20:29:30Z (GMT). No. of bitstreams: 1 GiocondaDiasRodriguesLeao_TESE.pdf: 44025376 bytes, checksum: 9da025324f9108141027f1f3a1cc3e16 (MD5) Previous issue date: 2013-05-17 / Background & Aims: HFE-associated Hereditary Hemochromatosis (HH) is one of the most frequent autosomal recessive disease in the caucasian population, caused by the high absorption and deposition of iron in several organs. This accumulation results in several clinical complications such as cirrhosis, arthritis, cardiopathies, diabetes, sexual disorders and skin darkening. Although most of the cases are homozygous individuals for the C282Y mutation, another two mutations, H63D and S65C, have been reported to be associated with milder forms of the disease. The objective is to avaluate the distribution of C282Y, H63D and S65C mutations in the HFE gene in patients with suspected HH in the state of Rio Grande do Norte, Brazil. Methods: Samples of peripheral blood were taken from 335 patients originating from Natal-RN, a city in northeastern Brazil with suspected of HH and which were screened for the HFE gene C282Y, H63D and S65C mutations, using molecular genetics assays (Polymerase Chain Reaction- Restriction Fragments Length Polymorphism). The main criterion for including such patients in the study was the increasing of persistent serum ferritin in individuals aged between 18 and 70 or older, both males and females. As to the exclusion criteria, individuals holding hemolytical anemia, talassemy and previously report of blood transfusion did not take part of the study. Results: Out of the 335 patients studied, 143 patients showed absence of mutation and 195 showed some kind of mutation in the HFE gene: 07/335 (2,08%) were homozigous C282Y, 25/335 heterozygous C282Y, 25/335 (7,46%) were homozigous H63D, 115/335 (34,32%) heterozygous H63D, 5/335 (1,48%) heterozygous S65D, 11/ 335 (3,28%) and were double heterozygous (H63D/C282Y). None patients were Homozygous S65D and S65D heterozygous (S65D/H63D and S65D/C282Y). Conclusions. The distribution of the HFE gene C282Y, H63D and S65C mutations found in our group matches the tendencies observed in other European countries. Due to the high prevalence of hemochromatosis, its seriousness and easy treatment, the genetic diagnosis of HH has become a dream, especially in the high risk group.