PROTECTIVE PROTEIN CATHEPSIN-A LOSS IN CULTURED-CELLS DERIVED FROM ANEARLY-INFANTILE FORM OF GALACTOSIALIDOSIS PATIENTS HOMOZYGOUS FOR THEA1184-G TRANSITION (Y395C MUTATION)/

Galactosialidosis is a human autosomal recessive lysosomal storage dis ease caused by a genetic defect of protective protein/cathepsin A (PPC A). 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 Y39 5C substitution The acid carboxypeptidase (cathepsin A) and lysosomal neuraminidase activities were markedly decreased in cultured fibroblas ts and chorionic villus cells derived from the patients, although the decrease in beta-galactosidase activity was less. Immunoblot and immun ocytochemical analyses showed that neither the precursor nor the matur e form of the PPCA gene product was present in the cultured cells, The Y395C mutation was revealed to cause the loss of the translated produ ct, that determines the severity of the clinical phenotype. (C) 1998 A cademic Press.