Research

Area 5

Genetics.

Team leader

Strategic objectives

Characterization of rare hereditary diseases in the clinical, cytogenetic and molecular contexts.

There are four main lines of research. Each line has the strategic objectives defined by the supporting research projects. In this context, the study of mental retardation (MR) and identification of the causal genetic factors are fundamented upon the application of high performance array CGH and Next Sequencing Generation (NSG) technologies. On the other hand, the study of fragile X–associated tremor/ataxia syndrome (FXTAS) aims to identify a biological marker allowing us to establish a presymptomatic diagnosis of FXTAS in carriers of the premutation in the FMR1 gene, based on study of the miRNA profile. Regarding the porphyrias, the strategic objective is to advance in our knowledge of the correlation genotype – phenotype: biochemical and clinical expression.

Main lines of research

  1. Identification of the genetic bases of mental retardation (MR) of genetic origin, both syndromic and non-syndromic, using the new NSG technologies.
    Application of massive sequencing to different groups of clinically well characterized MR will allow us to identify new genes and establish new molecular bases in MR. Application is also planned to the study of familial mental retardation and to sporadic cases of non-syndromic MR.
  2. Fragile X syndrome: Study of the pathologies associated with premutation of the FMR1 gene: POIFX (Premature ovarian insufficienciy), FXTAS (Fragile X Tremor Ataxia
    Syndrome), and fibromyalgia associated with the FMR1 gene. Study of the microRNA and ASFMR1 gene expression profiles as possible susceptibility factors for FXTAS.
  3. Detection of cryptic chromosomal imbalances and the identification of new phenotypes, based on cytogenetic - molecular techniques. One is conducted in the prenatal and postnatal diagnostic setting. The aim is to characterize chromosomal imbalances in fetuses with congenital anomalies and a normal karyotype, based on the use of CGH arrays.
  4. Study of the genotype-phenotype correlation and expression mechanisms of porphyria. The research lines aim to establish the following:

    • Advance in the study of the alterations in iron regulation and metabolism in skin and erythropoietic porphyria.
    • Investigate the role of modifier genes that modulate the clinical expression of erythropoietic porphyria.
    • Study of new serum and urine biomarkers of acute porphyria severity of use in clinical practice.

    The group will remain a member of the “European Porphyria Initiative” network as a reference center for the diagnosis, investigation and treatment of porphyria