Japanese-type adult galactosialidosis. A unique and common splice junction mutation causing exon skipping in the protective protein/carboxypeptidase gene.

Abstract

cDNA and genomic sequences coding for human protective protein/ carboxypeptidase were isolated and characterized. The cDNA sequence was identical with that reported by Galjart et al. (Cell 54: 755, 1988). Two clones hybridizing cDNA were isolated from the human chromosome 20 specific bacteriophage library, comprising the first 5 exons and the next 3 exons, respectively. The exon-intron organization was determined for these clones. Molecular analysis of Japanese adultform galactosialidosis patients revealed a common gene rearrangement: an A-to-G base substitution at the position 3 by downstream of exon 7, resulting in skipping of this exon in mRNA. All five cases in this study were found to be homozygous for this mutation. We conclude that this is a common gene mutation among the Japanese galactosialidosis patients of late onset (Japanese type).

Clinical and Molecular Heterogeneity in Hereditary β-Galactosidase Deficiency

“…We added more galactosialidosis patients after our previous report [14] and 10 patients with various clinical manifestations were studied. They were roughly classi fied into two major clinical forms: early onset (neonatal/ infantile) and late onset (juvenile/adult; table 3).…”

“…Two positive clones were isolated from a chromosome 20 library and found to contain the 5' side sequences including 8 exons [14]. Subsequently, the genomic DNA from late-onset patients was analyzed.…”

“…GMi-gangliosidosis has been recognized as a disease in infancy, but further clinical observations revealed some late-onset cases [11], Galactosialidosis patients have been found mainly in Japan at adult age, but some infants and chil dren are also reported in Japan and other countries [12]. Several gene mutations were detected and clear pheno type-genotype correlations were established in both dis eases in our laboratory [13,14], The results of molecular analysis of these two diseases are briefly reviewed and additional data are presented in this paper. …”

Galactosialidosis presenting as nonimmune fetal hydrops: a case report

“…Transmission is autosomal recessive. The gene has been located on 20q13.1 (Maire and Nivelon-Chevallier, 1981;Mueller et al, 1986), it has been cloned and several mutations have been identified (Shimmoto et al, 1990(Shimmoto et al, , 1993. Groener et al reported, in 2003, the first two Dutch cases of early-infantile GS, both presenting with neonatal ascites.…”

Structural and functional study of K453E mutant protective protein/cathepsin A causing the late infantile form of galactosialidosis

“…Based on the onset and severity of the disease, galactosialidosis is clinically divided into three subtypes: the early infantile, late infantile, and juvenile/ adult forms. Most patients with the juvenile/adult form of galactosialidosis are of Japanese origin, and they have a common a ϩ3 to g substitution at the exon 7/ intron 7 junction (SpDEx7) (Shimmoto et al 1990). The mutation results in a splicing defect and a decreased amount of PPCA mRNA.…”