title: Insertion of a T next to the donor splice site of intron 1 causes aberrantly spliced mRNA in a case of infantile GM1-gangliosidosis.
abstract: The lysosomal storage disorders GM1-gangliosidosis and Morquio B syndrome are caused by a complete or partial deficiency of acid beta-galactosidase. Here, we have characterized the mutation segregating in a family with two siblings affected by the severe infantile form of GM1-gangliosidosis. In total mRNA preparations derived from the patients' fibroblasts at least two aberrantly spliced beta-galactosidase transcripts (1 and 2) have been identified. Both transcripts contain a 20 nucleotide (nt) insertion derived from the 5' end of intron 1 of the beta-galactosidase gene. Furthermore, in transcript 2 sequences encoded by exon II are deleted during the splicing process. Comparison of the 20-nt insertion with wild-type intronic sequences indicated that in the genomic DNA of the patients an extra T nucleotide is present immediately downstream of the conserved GT splice donor dinucleotide of intron 1. Both patients are homozygous for the T nucleotide insertion. We propose that this single base insertion is the mutation responsible for aberrant splicing of beta-galactosidase pre-mRNA, giving rise to transcripts that cannot encode a normal protein.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Morrone
authors.forename: H
authors.initials: H
authors.lastname: Morreau
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhou
authors.forename: E
authors.initials: E
authors.lastname: Zammarchi
authors.forename: W J
authors.initials: WJ
authors.lastname: Kleijer
authors.forename: H
authors.initials: H
authors.lastname: Galjaard
authors.forename: A
authors.initials: A
authors.lastname: d'Azzo
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis / Q000235:genetics; D005347:Fibroblasts; D016537:Gangliosidosis, GM1 / Q000235:genetics*; D005796:Genes; D006801:Humans; D007231:Infant, Newborn; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics
chemical_list: D012333:RNA, Messenger