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Mucopolysaccharidosis type II in a female carrying a heterozygous stop mutation of the iduronate-2-sulfatase gene and showing a skewed X chromosome inactivation |
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| Authors: | Raul E. Piña-Aguilar Gerardo R. Zaragoza-Arévalo Isabella Rau Andreas Gal Miguel A. Alcántara-Ortigoza Mónica S. López-Martínez Yuritzi Santillán-Hernández |
| Affiliation: | 1. Department of Pediatrics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;2. Department of Endocrinology and Metabolism, Amsterdam Lysosome Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;3. Department of General Practice/Medical Ethics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;1. Adult Inherited Metabolic Disorders, The Mark Holland Metabolic Unit, Salford Royal Foundation NHS Trust, Ladywell NW2- 2nd Floor Room 112, Salford, Manchester, M6 8HD, United Kingdom;2. N.I. Regional Genetics Service, Level A, Belfast City Hospital, Lisburn Rd, Belfast BT9 7AB, United Kingdom |
| 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.Arg4431). 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. |
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