Abstract
Gaucher disease (GD) is an autosomal recessive disorder resulting from glucocerebrosidase (GC) deficiency due to mutations in the gene (GBA) coding for this enzyme. We have developed a strategy for analyzing the entire GBA coding region and applied this strategy to 48 unrelated Brazilian patients with GD. We used long-range PCR, genotyping based on the Taqman® assay, nested PCR, and direct DNA sequencing to define changes in the gene. We report here seven novel mutations that are likely to be harmful: S125N (c.491G>A), F213L (c.756T>G), P245T (c.850C>A), W378C (c.1251G>C), D399H (c.1312G>C), 982-983insTGC (c.980_982dupTGC), and IVS10+1G>T (c.1505+1G>T). The last alteration was found as a complex allele together with a L461P mutation. We also identified 24 different mutations previously reported by others. G377S was the third most frequent mutation among the patients included in this study, after N370S and L444P. Therefore, this mutation needs be included in preliminary screens of Brazilian GD patients. The identification of mutant GBA alleles is crucial for increasing knowledge of the GBA mutation spectrum and for better understanding of the molecular basis of GD.
Competing interests: None declared
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Acknowledgments
The authors are grateful to the patients and their families who kindly agreed to participate in this study. We also thank the physicians who referred patients to our laboratory and provided clinical information. The authors would also like to thank Thais Santa Rita for her laboratory technical assistance in this work. MS, JCC, RG, and MLSP were supported by CNPq, Brazil. HB was supported by CAPES, Brazil. The work was also supported by Brazilian Funding Agencies (CNPq, FAPERGS, and FIPE-HCPA) and by Genzyme do Brazil.
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Communicated by: Gregory M. Pastores
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Novel and rare mutations in the GBA gene of patients with Gaucher disease.
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Siebert, M., Bock, H., Michelin-Tirelli, K., Coelho, J.C., Giugliani, R., Saraiva-Pereira, M.L. (2012). Novel Mutations in the Glucocerebrosidase Gene of Brazilian Patients with Gaucher Disease. In: Zschocke, J., Gibson, K.M., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports – Case and Research Reports, 2012/6. JIMD Reports, vol 9. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_174
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DOI: https://doi.org/10.1007/8904_2012_174
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