Mucopolysaccharidosis type II (Hunter disease): identification and characterization of eight point mutations in the iduronate-2-sulfatase gene in Japanese patients

Human Mutation
K SukegawaTadao Orii

Abstract

Mucopolysaccharidosis type II (Hunter disease) is a lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. Varied clinical phenotypes of this disease have been described. To identify mutations in individual patients and to examine possible correlations between mutations and clinical phenotypes, we analyzed the iduronate-2-sulfatase gene in Japanese patients with different clinical phenotypes. Five missense mutations, S333L (severe), R468Q (severe), R468L (severe), W337R (intermediate), R48P (mild), and three nonsense mutations, W345X (severe), R443X (intermediate), Q531X (mild), were identified by the RT-PCR method. Transient expression in the enzyme-deficient fibroblasts revealed that all five missense mutant enzymes were synthesized as the normal-size precursor (73 kD), and the nonsense mutant enzymes were synthesized as truncated ones (W345X:54 kD, R443X:59 kD, and Q531X:69 kD), although stable mature enzymes (45-56 kD) were not detected by Western blot analysis. Furthermore, expression of the eight mutant cDNAs resulted in severe reductions of iduronate-2-sulfatase enzyme activity in comparison with a normal cDNA.

References

Dec 1, 1977·Proceedings of the National Academy of Sciences of the United States of America·F SangerA R Coulson
Jun 1, 1992·Human Genetics·M WehnertF H Herrmann
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P J WilsonJ J Hopwood
Jul 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·G BachE F Neufeld
Oct 1, 1973·Biochemical and Biophysical Research Communications·I SjöbergA Dorfman
Sep 1, 1993·Genomics·P J WilsonC P Morris
Jan 1, 1993·Human Mutation·R FroissartD Bozon

❮ Previous
Next ❯

Citations

Apr 20, 2011·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Raymond Y WangUNKNOWN ACMG Work Group on Diagnostic Confirmation of Lysosomal Storage Diseases
Jan 6, 1999·Archives of Disease in Childhood·E VafiadakiJ E Wraith
Mar 30, 2007·Acta Paediatrica. Supplement·Roseline FroissartIrène Maire
Oct 16, 2013·Molecular Genetics and Metabolism·A C Brusius-FacchinS Leistner-Segal
Oct 24, 2002·Biochimica Et Biophysica Acta·A DanieleP Di Natale
Jun 6, 2000·Biochimica Et Biophysica Acta·G R VillaniP Di Natale
Jun 10, 2003·American Journal of Medical Genetics. Part a·Verena RicciRosanna Gatti
Feb 28, 2019·European Journal of Pediatrics·Alessandra ZanettiRosella Tomanin
Sep 1, 2005·Journal of Human Genetics·Tomomi KatoYasuyuki Suzuki
Feb 8, 2003·Acta Paediatrica. Supplement·R FroissartI Maire
Jul 1, 1997·Journal of Inherited Metabolic Disease·W LissensI Liebaers

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.