Severe phenotype in MPS II patients associated with a large deletion including contiguous genes

Authors

  • Ana Carolina Brusius-Facchin,

    1. Medical Genetics Service, Hospital de Clínicas, Porto Alegre, RS, Brazil
    2. Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil
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  • Carolina Fischinger Moura De Souza,

    1. Medical Genetics Service, Hospital de Clínicas, Porto Alegre, RS, Brazil
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  • Ida Vanessa D. Schwartz,

    1. Medical Genetics Service, Hospital de Clínicas, Porto Alegre, RS, Brazil
    2. Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil
    3. Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
    4. BRAIN laboratory, Hospital de Clinicas, Porto Alegre, Rio Grande do Sul, Brazil
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  • Mariluce Riegel,

    1. Gene Therapy Center, Experimental Research Center, Hospital de Clínicas, Porto Alegre, Rio Grande do Sul, Brazil
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  • Maria Isabel Melaragno,

    1. Genetics Discipline, Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil
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  • Patrícia Correia,

    1. Department of Medical Genetics - Fernandes Figueira Institute – FIOCRUZ, Rio de Janeiro, Brazil
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  • Lúcia Marques Moraes,

    1. Department of Medical Genetics - Fernandes Figueira Institute – FIOCRUZ, Rio de Janeiro, Brazil
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  • Juan Llerena Jr.,

    1. Department of Medical Genetics - Fernandes Figueira Institute – FIOCRUZ, Rio de Janeiro, Brazil
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  • Roberto Giugliani,

    1. Medical Genetics Service, Hospital de Clínicas, Porto Alegre, RS, Brazil
    2. Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil
    3. Genetics Department, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
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  • Sandra Leistner-Segal

    Corresponding author
    1. Medical Genetics Service, Hospital de Clínicas, Porto Alegre, RS, Brazil
    2. Post Graduation Program in Medical Sciences, UFRGS, Porto Alegre, RS, Brazil
    3. BRAIN laboratory, Hospital de Clinicas, Porto Alegre, Rio Grande do Sul, Brazil
    • Medical Genetics Service – HCPA, Ramiro Barcelos, 2350 90035-903, Porto Alegre, RS, Brazil.

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  • How to Cite this Article: Brusius-Facchin AC, De Souza CFM, Schwartz IVD, Riegel M, Melaragno MI, Correia P, Moraes LM, Llerena J, Giugliani R, Leistner- Segal S. 2012. Severe phenotype in MPS II patients associated with a large deletion including contiguous genes. Am J Med Genet Part A. 158A:1055–1059.

Abstract

Hunter disease or mucopolysaccharidosis type II (MPS II) is an X-linked recessive lysosomal disorder caused by the deficiency of iduronate-2-sulfatase, which is involved in the catabolism of the glycosaminoglycans (GAGs) heparan and dermatan sulphate. Our aim was to analyze three patients with severe Hunter syndrome that showed a total deletion of the iduronate-2-sulphatase (IDS) gene, after exon by exon PCR. DNA was used as a template for PCR synthesis of IDS, FRAXA, FRAXE, and DXS1113 specific amplicons. The DNA analysis for all three patients demonstrated a complete deletion of IDS, FRAXA, and FRAXE contiguous genes. We further performed SNP-array to delineate the deletion breakpoints and to characterize the deletion extension in the different patients. The results indicated a ∼9.4 Mb deletion in Patient 1, a ∼3.9 Mb deletion of the Xq27.3–Xq28 and a ∼3.1 Mb duplication of the X q28 region in Patient 2 and a ∼41.8 Kb deletion in Patient 3. SNP-array was shown to be important to map for deletion breakpoints. A comprehensive molecular analysis in patients with Hunter syndrome, especially in the ones presenting the severe form, is important to the understanding of the genetic determinants of the phenotype and for the genetic counseling to be provided to the families. © 2012 Wiley Periodicals, Inc.

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