Abstract
Although Fabry disease is a rare lysosomal storage disorder, intensive research has been performed in the last decade in order to elucidate the pathogenesis, underlying mechanisms and the best treatment for this disorder. Despite this, the motto ‘10 years 10 doctors’ is still the reality mainly because of the difficulty to correlate between different signs and symptoms in one rare disease. Furthermore, there is no good correlation between phenotype-genotype and it is difficult if not impossible to predict which genotype will develop into a complete or partial Fabry phenotype and which females will remain asymptomatic and which will develop symptoms. This chapter will focus on describing the efforts that have been made over the years in order to try to correlate genotypes with specific phenotypes as well as modifier genes that might help predicting future symptoms of patients with Fabry disease.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Bishop DF, Kornreich R, Desnick RJ (1988) Structural organization of the human alpha-galactosidase A gene: further evidence for the absence of a 3’ untranslated region. Proc Natl Acad Sci USA 85:3903–3907
Garman SC, Garboczi DN (2004) The molecular defect leading to Fabry disease: structure of human alpha-galactosidase. J Mol Biol 337:319–335
Cilmi SA, Karalius BJ, Choy W, Smith RN, Butterton JR (2006) Fabry disease in mice protects against lethal disease caused by Shiga toxin-expressing enterohemorrhagic Escherichia coli. J Infect Dis 194:1135–1140
Hartmann C, John AL, Klaes R et al (2004) Large BRCA1 gene deletions are found in 3% of German high-risk breast cancer families. Hum Mutat 24:534
Schouten JP, McElgunn CJ, Waaijer R, Wijnenburg DZ, Diepvens F, Pals G (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation dependent probe amplification. Nucleic Acids Res 30:e57
Schirinzi A, Centra M, Prattichizzo C et al (2008) Identification of GLA gene deletions in Fabry patients by Multiplex Ligation-dependent Probe Amplification (MLPA). Mol Genet Metab 94:382–385
Filoni C, Caciotti A, Carraresi L et al (2008) Unbalanced GLA mRNAs ratio quantified by real-time PCR in Fabry patients’ fibroblasts results in Fabry disease. Eur J Hum Genet 16:1311–1317
Fervenza FC, Torra R, Lager DJ (2008) Fabry disease: an under-recognized cause of proteinuria. Kidney Int 73:1193–1199
Ishii S, Nakao S, Minamikawa-Tachino R et al (2002) Alternative splicing in the alpha-galactosidase A gene: increased exon inclusion results in the Fabry cardiac phenotype. Am J Hum Genet 70:994–1002
Altarescu G, Moore DF, Schiffmann R (2005) Effect of genetic modifiers on cerebral lesions in Fabry disease. Neurology 64:2148–2150
Shen Y, Bodary PF, Vargas FB et al (2006) Alpha-galactosidase A deficiency leads to increased tissue fibrin deposition and thrombosis in mice homozygous for the factor V Leiden mutation. Stroke 37:1106–1108
Rohard I, Schaefer E, Kampmann C, Beck M, Gal A (2008) Association between polymorphisms of endothelial nitric oxide synthase gene (NOS3) and left posterior wall thickness (LPWT) of the heart in Fabry disease. J Inherit Metab Dis
Blaydon D, Hill J, Winchester B (2001) Fabry disease: 20 novel GLA mutations in 35 families. Hum Mutat 18:459
Eng CM, Resnick-Silverman LA, Niehaus DJ, Astrin KH, Desnick RJ (1993) Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease. Am J Hum Genet 53:1186–1197
Bekri B, Enica A, Ghafari T et al (2005) Fabry disease in patients with end-stage renal failure: the potential benefits of screening. Nephron Clin Pract 101:33–38
Eldos M, Nemeth K, Toth B et al (2008) Novel sequence variants of the a-galactosidase A gene in patients with Fabry disease. Mol Genet Metab 95:224–228
Teitcher M, Weinerman S, Whybra C et al (2008) Genetic polymorphisms of vitamin D receptor (VDR) in Fabry disease. Genetica 134:377–383
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2010 Springer Netherlands
About this chapter
Cite this chapter
Altarescu, G. (2010). Clinically Relevant Examples of Genotype–Phenotype Correlation. In: Elstein, D., Altarescu, G., Beck, M. (eds) Fabry Disease. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-9033-1_5
Download citation
DOI: https://doi.org/10.1007/978-90-481-9033-1_5
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-9032-4
Online ISBN: 978-90-481-9033-1
eBook Packages: MedicineMedicine (R0)