Molecular basis of mucopolysaccharidosis type VII: replacement of Ala619 in beta-glucuronidase with Val

Gene
S TomatsuT Orii

Abstract

We have identified a mutation causing beta-glucuronidase (beta Gl) deficiency in a 6-year-old girl with mucopolysaccharidosis type VII. Enzyme assay of lysates of a girl's lymphocytes or cultured fibroblasts showed little residual activity and a normal beta Gl-specific mRNA level, as revealed by Northern-blot analysis. Sequencing of the full-length mutated cDNA revealed a C----T transition, an event causing a single Ala619----Val change (we designated this variant beta GGifu). This change is detected by loss of the cleavage site for the enzyme Fnu4HI in the mutated cDNA. On the basis of the loss of Fnu4HI restriction site, the patient was shown to be a homozygote with the beta GGifu mutation and her parents and brother were heterozygotes. This mutation disrupts a functional domain consisting of a region of sequence highly conserved among human, rat and bacterial beta Gls, and it reduces the enzyme activity, as tested by transfection of COS cells with expression vectors harboring the mutated cDNA.

References

Jan 1, 1978·Annual Review of Biochemistry·P Y Chou, G D Fasman
Nov 30, 1988·Biochemical and Biophysical Research Communications·A OshimaY Suzuki
Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·Y NishimuraR Andy
Feb 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·A OshimaR A Gravel
Feb 1, 1986·Analytical Biochemistry·M Hattori, Y Sakaki
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·R A JeffersonD Hirsh
Mar 11, 1983·Nucleic Acids Research·H Luthman, G Magnusson

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Citations

Jan 1, 1994·Prenatal Diagnosis·A H Fensom, P F Benson
Jan 1, 1991·Journal of Inherited Metabolic Disease·S FukudaT Orii
Oct 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shunji TomatsuWilliam S Sly
Feb 19, 2009·Human Mutation·Shunji TomatsuWilliam S Sly
Feb 17, 2017·Prenatal Diagnosis·Francyne KubaskiShunji Tomatsu
Jan 18, 2019·American Journal of Medical Genetics. Part a·Piranit N KantaputraPranoot Tanpaiboon
Feb 14, 2021·Diagnostics·Betul ÇelikShaukat A Khan
Apr 24, 1995·Biochimica Et Biophysica Acta·V Gieselmann

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