title: Severe phenotype in MPS II patients associated with a large deletion including contiguous genes.
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.
authors.affiliation: Medical Genetics Service, Hospital de Clínicas, Porto Alegre, RS, Brazil.
authors.forename: Ana Carolina
authors.initials: AC
authors.lastname: Brusius-Facchin
authors.forename: Carolina Fischinger Moura
authors.initials: CF
authors.lastname: De Souza
authors.forename: Ida Vanessa D
authors.initials: IV
authors.lastname: Schwartz
authors.forename: Mariluce
authors.initials: M
authors.lastname: Riegel
authors.forename: Maria Isabel
authors.initials: MI
authors.lastname: Melaragno
authors.forename: Patrícia
authors.initials: P
authors.lastname: Correia
authors.forename: Lúcia Marques
authors.initials: LM
authors.lastname: Moraes
authors.forename: Juan
authors.initials: J
authors.lastname: Llerena
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Sandra
authors.initials: S
authors.lastname: Leistner-Segal
mesh_terms: D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics; D016532:Mucopolysaccharidosis II / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
chemical_list: D007066:Iduronate Sulfatase