DEVELOPMENT OF MOLECULAR DIAGNOSTICS FOR DETECTION OF LARGE DELETIONS AND INSERTIONS IN MUCOPOLYSACCHARIDOSES (TYPE I, II AND VI).

• Grant number: 12/14041-8
• Support Opportunities: Scholarships in Brazil - Master
• Start date: September 01, 2012
• End date: August 31, 2013
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: João Bosco Pesquero
• Grantee: Fabiana Louise Teixeira Motta
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Mucopolysaccharidoses (MPSs) are rare lysosomal storage diseases. MPSs are hereditary, progressive, chronic, multisystemic and there are many degrees of severity. They are caused by low or absent activity of enzymes that metabolize the glycosaminoglycans (GAGs). This enzymatic inefficiency leads to accumulation of GAGs partially or not degraded within the lysosomes. In consequence, there is a sequence of damaging effects influencing from cells to organs.There are treatments to alleviate/delay the symptoms of MPS patients. The success of these therapies is related to early medical intervention. Because it is a complex disease, it is necessary to run some laboratory tests to confirm a final diagnosis. In addition to knowing type of MPS disease, it may be necessary to establish the MPS subtype in order to choose the best treatment available. The MPS subtypes are correlated to disease severity and are best determined by investigating the mutations per se.DNA sequencing is considered the gold standard for determination of mutations in cases of inherited diseases with many causal mutations, such as MPSs. However, the analysis involves only the amplification of fragments containing the exons and its flanking regions and thus may fail to detect large deletions and insertions potentially leading to misdiagnosis. This could be avoided quantifying exons by fragment analysis instead. The aim of this project is to develop a technique for quantifying exons related to MPS type I, II and VI, expectedly improving the accuracy of the existing molecular diagnostics techniques currently in use.