Richard_1998_Hum.Mutat_11_461

Reference

Title : Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A\/protective protein gene - Richard_1998_Hum.Mutat_11_461
Author(s) : Richard C , Tranchemontagne J , Elsliger MA , Mitchell GA , Potier M , Pshezhetsky AV
Ref : Hum Mutat , 11 :461 , 1998
Abstract :

Galactosialidosis is a recessively inherited lysosomal storage disease characterized by the combined deficiency of neuraminidase and beta-galactosidase secondary to the genetic deficiency of cathepsin A/protective protein. In lysosomes, cathepsin A forms a high-molecular-weight complex with beta-galactosidase and neuraminidase that protects these enzymes against intralysosomal proteolysis. In a patient affected with late infantile form of galactosialidosis, we found two new cathepsin A mutations, a two-nucleotide deletion, c517delTT and an intronic mutation, IVS8+9C-->G resulting in abnormal splicing and a five-nucleotide insertion in the cathepsin A cDNA. Both mutations cause frameshifts and result in the synthesis of truncated cathepsin A proteins, which, as suggested by structural modeling, are incapable of dimerization, complex formation, and catalysis. However, enzymatic assays, gel-filtration, and Western blot analysis of the patient's cultured skin fibroblast extracts showed the presence of a small amount of normal-size, catalytically active cathepsin A and cathepsin A-beta-galactosidase 680 kDa complex, suggesting that a low amount of cathepsin A mRNA is spliced normally and produces the wild-type protein. This may contribute to the relatively mild phenotype of the patient and illustrates the importance of critically comparing molecular results with clinical and biochemical phenotypes.

PubMedSearch : Richard_1998_Hum.Mutat_11_461
PubMedID: 9603439
Gene_locus related to this paper: human-CTSA

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Citations formats

Richard C, Tranchemontagne J, Elsliger MA, Mitchell GA, Potier M, Pshezhetsky AV (1998)
Molecular pathology of galactosialidosis in a patient affected with two new frameshift mutations in the cathepsin A\/protective protein gene
Hum Mutat 11 :461

Richard C, Tranchemontagne J, Elsliger MA, Mitchell GA, Potier M, Pshezhetsky AV (1998)
Hum Mutat 11 :461