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.
|Number of pages||4|
|Journal||European Journal of Medical Genetics|
|Early online date||8 Dec 2012|
|Publication status||Published - Mar 2013|
|Event||12th International Symposium on MPS and Related Diseases - Noordwijkerhout, Netherlands|
Duration: 28 Jun 2012 → 1 Jul 2012
Bibliographical noteWe are very grateful to the family of the patient that, in spite of the pain of having their daughter suffering of MPS and later the pain of losing her, cooperated with us and agreed to the publication of this case.
We thank the Laboratory of Genetics from CMN “20 de Noviembre” ISSSTE, especially to M. Concepcion Yerena de Vega, for cytogenetic analysis of the case. We are also grateful to Dr. Joaquín Carrillo-Farga from Instituto de Hematopatologia, Mexico for his expertise in blood smear analysis and to Dr. Paula A. Rozenfeld from LISIN, Argentina for enzymatic analysis.
- Hunter syndrome
- X-linked disease