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Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene

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JIMD Reports – Case and Research Reports, 2012/6

Part of the book series: JIMD Reports ((JIMD,volume 9))

Abstract

Chitotriosidase (ChT) is a human chitinase secreted by activated macrophages and its activity is used in therapeutic monitoring of Gaucher disease (GD), the most common lysosomal storage disease. About 6% of the population is homozygous for a duplication of 24 bp in exon 11 of the CHIT1 gene (dup24), which is the main polymorphism that results in the absence of ChT. As ChT enzyme activity can be used as a biomarker in GD, it is important to know the CHIT1 genotype of each patient. In this study, ChT activity and CHIT1 genotype were evaluated in 33 GD type 1 patients under treatment in the state of Minas Gerais, Brazil, and compared to healthy controls. As expected, the enzyme activity was found to be higher in GD type 1 patients than in healthy subjects. Four patients had no ChT activity. Their genotype revealed three patients (9%) homozygous for dup24 allele and one patient with two polymorphisms in exon 11: G354R and a 4 bp deletion at the exon-intron 11 boundary (g.16993_16996delGAGT), the later described for the first time in literature. Two other patients with lower ChT activity presented a polymorphism in exon 4 (c.304G>A, p.G102S), without dup24 allele. In conclusion, this study demonstrated that ChT activity can be used for therapeutic monitoring in 82% of GD patients of the state of Minas Gerais, Brazil.

Competing interests: None declared

Co-senior authors: Ana Lúcia B Godard Eugênia R Valadares

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Acknowledgments

We thank all the patients and control group for participation and for their cooperation, Prof. Luiz Alberto Cury, from Department of Physics – UFMG, Prof. Miguel Pocoví and Pilar Alfonso Palacín, from the Laboratorio de Bioquímica y Biología Celular y Molecular – University of Zaragoza, Spain, and Mrs. Annelie Schlenger, from the Biochemical Laboratory at the Children’s Hospital at University of Mainz, Germany, for the valuable discussions; the physicians of the Hematology Clinic at HC-UFMG for the good interaction with us in the laboratory; the Fundação de Amparo a Pesquisa do Estado de Minas Gerais for the financial support and master degree scholarship.

Author information

Authors and Affiliations

  1. Laboratório de Genética Animal e Humana, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Talita E R Adelino, Aretta A A Gomes, Adriana A Torres, Daniel A S Silva & Ana Lúcia B Godard

  2. Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Gustavo G Martins, Vinícius D O Xavier, João Paulo O Guimarães, Sérgio S S Araújo, Rachel A F Fernandes, Maria Christina L A Oliveira & Eugênia R Valadares

  3. Departamento de Propedêutica Complementar, Universidade Federal de Minas Gerais, Avenida Professor Alfredo Balena190, 31130-100, Belo Horizonte, Minas Gerais, Brazil

    Eugênia R Valadares

  4. Departamento de Propedêutica Complementar, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil

    Eugênia R Valadares

Authors
  1. Talita E R Adelino
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  2. Gustavo G Martins
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  3. Aretta A A Gomes
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  4. Adriana A Torres
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  5. Daniel A S Silva
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  6. Vinícius D O Xavier
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  7. João Paulo O Guimarães
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  8. Sérgio S S Araújo
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  9. Rachel A F Fernandes
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  10. Maria Christina L A Oliveira
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  11. Ana Lúcia B Godard
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  12. Eugênia R Valadares
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Corresponding author

Correspondence to Eugênia R Valadares .

Editor information

Editors and Affiliations

  1. Sektionen für Humangenetik und Klinische, Medizinische Universität Innsbruck, Innsbruck, Austria

    Johannes Zschocke (Editors-in-Chief) (Editors-in-Chief)

  2. Biological Sciences, Michigan Technological University, Houghton, Michigan, USA

    K. Michael Gibson (Editors-in-Chief) (Editors-in-Chief)

  3. Department of Biochemistry Genetics Unit, University of Oxford, Oxford, UK

    Garry Brown (Editors) (Editors)

  4. Medical Center Department of Pediatrics IGMD, Radboud University Nijmegen, Nijmegen, Netherlands

    Eva Morava (Editors) (Editors)

  5. Center for Child and Adolescent Medicine, Heidelberg University Hospital, Heidelberg, Germany

    Verena Peters (Managing Editor) (Managing Editor)

Additional information

Communicated by: Gregory M. Pastores

Appendices

Synopsis

Biochemical and molecular chitotriosidase profiles in Brazilian patients of Minas Gerais state, affected by Gaucher disease type 1, including the discovery of a new mutation in CHIT1 gene, are reported.

Conflict of Interest

None declared

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Adelino, T.E.R. et al. (2012). Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene. 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_184

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  • DOI: https://doi.org/10.1007/8904_2012_184

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  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-35517-2

  • Online ISBN: 978-3-642-35518-9

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