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.

Insertion of a T Next to the Donor Splice Site of Intron 1 Causes Aberrantly Spliced mRNA in a Case of Infantile GM1-Gangliosidosis / A. MORRONE; H. MORREAU; X.Y. ZHOU; E. ZAMMARCHI; W.J. KLEIJER; H. GALJAARD; A. D'AZZO. - In: HUMAN MUTATION. - ISSN 1059-7794. - STAMPA. - 3 (2):(1994), pp. 112-120.

Insertion of a T Next to the Donor Splice Site of Intron 1 Causes Aberrantly Spliced mRNA in a Case of Infantile GM1-Gangliosidosis.

MORRONE, AMELIA;ZAMMARCHI, ENRICO;
1994

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.
1994
3 (2)
112
120
A. MORRONE; H. MORREAU; X.Y. ZHOU; E. ZAMMARCHI; W.J. KLEIJER; H. GALJAARD; A. D'AZZO
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/216142
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