title: A 3' splice site consensus sequence mutation in the intron 3 of the alpha-galactosidase A gene in a patient with Fabry disease.
abstract: Fabry disease is an X-linked disorder accompanied with accumulation of glycosphingolipids resulting from the deficient activity of the lysosomal hydrolase, alpha-galactosidase A (alpha-GalA). In the present study, mRNA for alpha-GalA in fibroblasts from an 11-year-old Japanese patient with Fabry disease was examined using the reverse transcriptase-polymerase chain reaction (PCR). The shorter message of alpha-GalA was demonstrated in this patient when compared with the normal control. The complete deletion of exon 4 in the mRNA for alpha-GalA in the patient was disclosed by analysis of cDNA with restriction enzyme digestion and asymmetrical PCR sequencing. The direct sequencing of the genomic DNA demonstrated a single base substitution (G----A) at the 3' end of the consensus sequence of intron 3. This mutation destroyed a splice site in the alpha-GalA, which produced a mutant allele. It was also shown that the mother of the patient had this mutant as well as normal alleles as a heterozygote.
authors.affiliation: Department of Pediatrics, School of Medicine, Kanazawa University, Ishikawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yokoi
authors.forename: K
authors.initials: K
authors.lastname: Shinoda
authors.forename: I
authors.initials: I
authors.lastname: Ohno
authors.forename: K
authors.initials: K
authors.lastname: Kato
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
authors.forename: N
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D002648:Child; D002872:Chromosome Deletion; D002874:Chromosome Mapping; D016384:Consensus Sequence / Q000235:genetics*; D005091:Exons; D000795:Fabry Disease / Q000201:enzymology / Q000235:genetics*; D005696:Galactosidases / Q000235:genetics*; D005796:Genes; D006801:Humans; D007438:Introns; D008297:Male; D009154:Mutation; D012326:RNA Splicing / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D005696:Galactosidases