NAGLU mutations underlying Sanfilippo syndrome type B

American Journal of Human Genetics
A SchmidtchenE F Neufeld

Abstract

Sanfilippo syndrome type B (mucopolysaccharidosis III B) is a rare autosomal recessive disease caused by deficiency of alpha-N-acetylglucosaminidase, one of the enzymes required for the lysosomal degradation of heparan sulfate. The gene for this enzyme, NAGLU, recently was isolated, and several mutations were characterized. We have identified, in amplified exons from nine fibroblast cell lines derived from Sanfilippo syndrome type B patients, 10 additional mutations: Y92H, P115S, Y140C, E153K, R203X, 650insC, 901delAA, P358L, A664V, and L682R. Four of these mutations were found in homozygosity, and only two were seen in more than one cell line. Thus, Sanfilippo syndrome type B shows extensive molecular heterogeneity. Stable transfection of Chinese hamster ovary cells, by cDNA mutagenized to correspond to the NAGLU missense mutations, did not yield active enzyme, demonstrating the deleterious nature of the mutations. Nine of the 10 amino acid substitutions identified to date are clustered near the amino or the carboxyl end of alpha-N-acetylglucosaminidase, suggesting a role for these regions in the transport or function of the enzyme.

References

Oct 1, 1985·Analytical Biochemistry·P K SmithD C Klenk
Sep 1, 1993·Archives of Disease in Childhood·M A Cleary, J E Wraith
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·H G ZhaoE F Neufeld
Sep 1, 1996·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Z ZhaoC C Lee

❮ Previous
Next ❯

Citations

Sep 10, 2005·Journal of Inherited Metabolic Disease·C E BeesleyB G Winchester
Sep 21, 2010·Journal of Inherited Metabolic Disease·Marlies J ValstarFrits A Wijburg
Sep 15, 2012·Journal of Inherited Metabolic Disease·Laura M PollardTim C Wood
Oct 6, 2001·Pediatric Neurology·R BaroneL Pavone
Jan 16, 1999·Current Opinion in Biotechnology·J D Terwilliger, K M Weiss
Apr 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Elizabeth Ficko-BleanAlisdair B Boraston
Dec 10, 2013·Orphanet Journal of Rare Diseases·Verónica DelgadilloMercedes Pineda
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·H H LiE F Neufeld
Apr 9, 2008·Journal of Inherited Metabolic Disease·M J ValstarF A Wijburg
Oct 18, 2011·Journal of Inherited Metabolic Disease·Guglielmo R D VillaniPaola Di Natale
Feb 27, 2004·Clinical Genetics·C BeesleyH Michelakakis
Jan 5, 2011·American Journal of Medical Genetics. Part a·Bénédicte HéronMarc Tardieu
Jan 4, 2001·Molecular Genetics and Metabolism·W H YuE F Neufeld
Mar 10, 2001·Protein Expression and Purification·B WeberG Yogalingam
Feb 28, 2019·European Journal of Pediatrics·Alessandra ZanettiRosella Tomanin
Jul 20, 2016·Science China. Life Sciences·Jian Xiong, Michael X Zhu
Jun 9, 2018·Clinical Case Reports·Dineshani HettiarachchiVajira H W Dissanayake
Jan 15, 2005·The Biochemical Journal·Paola Di NataleGuglielmo R D Villani
Feb 14, 2021·Diagnostics·Betul ÇelikShaukat A Khan
Feb 10, 2020·The Journal of Molecular Diagnostics : JMD·Alessandra ZanettiRosella Tomanin
Feb 26, 2019·Journal of Structural Biology·Gabriel BirraneMuthuraman Meiyappan

❮ 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.