Genotype-phenotype correlation in Fabry disease

• Grant number: 18/04776-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2018
• End date: September 30, 2019
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: João Bosco Pesquero
• Grantee: Henrique Lage Ferreira Ferrer
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Fabry disease (FD) is an inborn error of metabolism, linked to the X chromosome, with a progressive and inherited character, due to ±-galactosidase A enzyme deficiency, responsible for globotriaosylceramide (Gb3) degradation. Patients with FD show progressive Gb3 storage in lysosomes of endothelium cells, especially in tissues such as kidneys, eyes, skin, heart and brain. From different origins, acroparesthesia, angiokeratomas, cold and heat intolerance - hypohidrosis, memory loss and proteinuria may be highlighted as symptoms with a common denominator. Based on clinical report, FD can be classified into two different ways: classical and atypical. Each patient's phenotype might be determined by the type of mutation, depending on enzymatic residual activity. However, genotype-phenotype correlation is not well established. Knowledge about GLA mutations is important to build a solid understanding on the nature and evolution of Fabry disease, and clinical correlations are essential to bring this molecular comprehension to medical conduct. In this study, held at Unifesp, genomic DNA was extracted from peripheral blood. Fragments containing all the seven exons and the exon/intron boundaries were amplified by PCR and sequenced by Sanger sequencing. The objective of this study is to perform a genotype-phenotype correlation involving 11 different mutations found after DNA analysis. One of these mutations is a new duplication of 14 nucleotides from position 72 in exon 1 (c.59_72dupCCCTCGTTTCCTGG), which produces a premature stop codon (p.D25fsX125). Awareness about basic mechanisms is essential to clinical application, and facing this situation, it is necessary to aim at a better treatment of FD.