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: A Morrone, H Morreau, X Y Zhou, E Zammarchi, W J Kleijer, H Galjaard, A d'Azzo
• Journal: Human mutation (Hum Mutat) Vol. 3 Issue 2 Pg. 112-20 ( 1994) ISSN: 1059-7794 [Print] United States
• PMID: 8199591 (Publication Type: Case Reports, Journal Article)

Chemical References

• RNA, Messenger

Topics

• Base Sequence
• Cells, Cultured
• DNA Mutational Analysis
• Female
• Fetal Diseases (diagnosis, genetics)
• Fibroblasts
• Gangliosidosis, GM1 (genetics)
• Genes
• Humans
• Infant, Newborn
• Introns
• Male
• Molecular Sequence Data
• Polymerase Chain Reaction
• Pregnancy
• Prenatal Diagnosis
• RNA Splicing
• RNA, Messenger (genetics)