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Exome sequencing in primary iron overload

Grant number: 11/18702-6
Support type:Regular Research Grants
Duration: December 01, 2011 - November 30, 2013
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Alexandre da Costa Pereira
Grantee:Alexandre da Costa Pereira
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers: Isolmar Tadeu Schettert ; José Eduardo Krieger ; Paulo Caleb Júnior de Lima Santos


Hereditary hemochromatosis (HH) is an autosomal recessive disorder characterized by enhanced intestinal absorption of dietary iron. Without therapeutic intervention, iron overload leads to multiple organ damage such as liver cirrhosis, cardiomyopathy, diabetes, arthritis, hypogonadism and skin hyperpigmentation. Most HH patients carry HFE mutant genotypes: homozygosity for p.C282Y or p.C282Y/p.H63D compound heterozygosity. In addition to HFE gene mutations, mutations in the genes that encode hemojuvelin (HJV), hepcidin (HAMP), transferrin receptor 2 (TFR2) and ferroportin (SLC40A1) have been associated with regulation of iron homeostasis and development of HH. In addition to the molecular epidemiology of HH being different in Brazil compared with Northern European countries, studies from our group reported that some patients with iron overload, whose secondary causes were excluded and extensively phenotyped and genotyped, were not carriers of mutations in the genes cited above. Thus, it is important to identify genetic characteristics of this population, since this approach can achieve the identification of new mutations and new genes involved in iron homeostasis. In this scenario, our main aim is to search for causative mutations in Brazilian patients with primary iron overload, whose secondary causes were excluded, and whithout any mutation identified in the cited genes. Exome sequencing will be carried for 10 patient samples from the Blood Center of Santa Casa de São Paulo. Expected results are the identification of new gene mutations that may explain the phenotype on the studied individuals. After, this information may be checked in other patients with similar findings and; thus, become useful for the understanding of the pathophysiology of HH and the genetic diagnosis of Brazilian patients. (AU)