Article
Severe phenotype in MPS II patients associated with a large deletion including contiguous genes
Registro en:
BRUSIUS-FACHIN, Ana Carolina et al. Severe phenotype in MPS II patients associated with a large deletion including contiguous genes. American Journal of Medical Genetics, Hoboken, v. 158A, p. 1055–1059, 2012.
0148-7299
10.1002/ajmg.a.35271
Autor
Brusius-Facchin, Ana Carolina
Souza, Carolina Fischinger Moura De
Schwartz, Ida Vanessa D.
Riegel, Mariluce
Melaragno, Maria Isabel
Correia, Patrícia
Moraes, Lúcia Marques
Llerena Junior, Juan Clinton
Giugliani, Roberto
Leistner-Segal
Resumen
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 catabolismof 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 9.4Mb deletion in Patient 1, a 3.9Mb deletion of the Xq27.3–Xq28 and a 3.1Mb 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.