Molecular and phenotypic variation in patients with severe Hunter syndrome.

TitleMolecular and phenotypic variation in patients with severe Hunter syndrome.
Publication TypeJournal Article
Year of Publication1997
AuthorsTimms, KM, Bondeson, ML, Ansari-Lari, MA, Lagerstedt, K, Muzny, DM, Dugan-Rocha, SP, Nelson, DL, Pettersson, U, Gibbs, RA
JournalHum Mol Genet
Date Published1997 Mar
KeywordsChromosome Mapping, Cloning, Molecular, Electrophoresis, Agar Gel, Gene Deletion, Gene Expression, Gene Rearrangement, Humans, Iduronate Sulfatase, Male, Molecular Sequence Data, Mucopolysaccharidosis II, Nuclear Proteins, Phenotype, Polymerase Chain Reaction, Proteins, Pseudogenes, Recombination, Genetic, Seizures, Trans-Activators, X Chromosome

Severe Hunter syndrome is a fatal X-linked lysosomal storage disorder caused by iduronate-2-sulphatase (IDS) deficiency. Patients with complete deletion of the IDS locus often have atypical phenotypes including ptosis, obstructive sleep apnoea, and the occurrence of seizures. We have used genomic DNA sequencing to identify several new genes in the IDS region. DNA deletion patients with atypical symptoms have been analysed to determine whether these atypical symptoms could be due to involvement of these other loci. The occurrence of seizures in two individuals correlated with a deletion extending proximal of IDS, up to and including part of the FMR2 locus. Other (non-seizure) symptoms were associated with distal deletions. In addition, a group of patients with no variant symptoms, and a characteristic rearrangement involving a recombination between the IDS gene and an adjacent IDS pseudogene (IDS psi), showed normal expression of loci distal to IDS. Together, these results identify FMR2 as a candidate gene for seizures, when mutated along with IDS.

Alternate JournalHum Mol Genet
PubMed ID9147653
Grant ListP30 HG00210 / HG / NHGRI NIH HHS / United States
R01 HG00823 / HG / NHGRI NIH HHS / United States

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