title: Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation.
abstract: We report a Mexican girl showing the full blown clinical picture of mucopolysaccharidosis type II (MPSII). Iduronate-2-sulfatase (IDS) activity was low and she carried a heterozygous de novo c.1327C>T transition in exon 9, that changes codon 443 for a premature stop (TGA; p.Arg443(*)). Analysis of X-chromosome inactivation in androgen receptor (AR) locus showed a highly skewed ratio of 92:8 suggesting a functional hemizygosity with dominant expression of the mutant IDS and explaining the disease manifestation. This is one of the rare cases of females affected by MPSII due to the combined effect of a skewed X-chromosome inactivation and a de novo IDS mutation. We recommend that clinicians should consider the diagnosis of MPSII even in a girl without positive family history for this condition.
authors.affiliation: Medical Genetics Department, Centro Médico Nacional 20 de Noviembre, ISSSTE, México City, Mexico.
authors.forename: Raul E
authors.initials: RE
authors.lastname: Piña-Aguilar
authors.forename: Gerardo R
authors.initials: GR
authors.lastname: Zaragoza-Arévalo
authors.forename: Isabella
authors.initials: I
authors.lastname: Rau
authors.forename: Andreas
authors.initials: A
authors.lastname: Gal
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alcántara-Ortigoza
authors.forename: Mónica S
authors.initials: MS
authors.lastname: López-Martínez
authors.forename: Yuritzi
authors.initials: Y
authors.lastname: Santillán-Hernández
mesh_terms: D002675:Child, Preschool; D005091:Exons; D005260:Female; D006579:Heterozygote; D006801:Humans; D007066:Iduronate Sulfatase / Q000235:genetics*; D016532:Mucopolysaccharidosis II / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation; D011944:Receptors, Androgen / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D007066:Iduronate Sulfatase