Protective protein/cathepsin A loss in cultured cells derived from an early-infantile form of galactosialidosis patients homozygous for the A1184-G transition (Y395C mutation).

Abstract

Galactosialidosis is a human autosomal recessive lysosomal storage disease caused by a genetic defect of protective protein/cathepsin A (PPCA). The patients in a Japanese family with the severe early-infantile form of galactosialidosis were revealed to be homozygous for the A1184-G transition in the PPCA gene in both alleles, which leads to the Y395C substitution. The acid carboxypeptidase (cathepsin A) and lysosomal neuraminidase activities were markedly decreased in cultured fibroblasts and chorionic villus cells derived from the patients, although the decrease in beta-galactosidase activity was less. Immunoblot and immunocytochemical analyses showed that neither the precursor nor the mature form of the PPCA gene product was present in the cultured cells. The Y395C mutation was revealed to cause the loss of the translated product, that determines the severity of the clinical phenotype.

• Authors: K Itoh, M Shimmoto, K Utsumi, N Mizoguchi, N Miharu, K Ohama, H Sakuraba
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 247 Issue 1 Pg. 12-7 (Jun 09 1998) ISSN: 0006-291X [Print] United States
• PMID: 9636645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies
• Tyrosine
• Carboxypeptidases
• CTSA protein, human
• Cathepsin A
• Cysteine

Topics

• Amino Acid Substitution (genetics)
• Antibodies (analysis)
• Carboxypeptidases (genetics, immunology, metabolism)
• Cathepsin A
• Cells, Cultured
• Cysteine (genetics)
• Female
• Fluorescent Antibody Technique, Indirect
• Genotype
• Homozygote
• Humans
• Immunoblotting
• Infant
• Lysosomal Storage Diseases (enzymology, genetics)
• Lysosomes (enzymology)
• Male
• Pedigree
• Point Mutation
• Tyrosine (genetics)