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Insertion of a T next to the donor splice site of intron 1 causes aberrantly spliced mRNA in a case of infantile G M1 ‐gangliosidosis
Author(s) -
Morrone Amelia,
Morreau Hans,
Zhou Xiao Yan,
Zammarchi Enrico,
Kleijer Wim J.,
Galjaard Hans,
d'Azzo Alessandra
Publication year - 1994
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.1380030205
Subject(s) - intron , exon , biology , rna splicing , genetics , splice site mutation , gene , splice , mutation , microbiology and biotechnology , insertion , alternative splicing , genomic dna , nucleotide , messenger rna , base pair , exon skipping , rna
The lysosomal storage disorders G M1 ‐gangliosidosis and Morquio B syndrome are caused by a complete or partial deficiency of acid β‐galactosidase. Here, we have characterized the mutation segregating in a family with two siblings affected by the severe infantile form of G M1 ‐gangliosidosis. In total mRNA preparations derived from the patients' fibroblasts at least two aberrantly spliced β‐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 β‐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 β‐galactosidase pre‐mRNA, giving rise to transcripts that cannot encode a normal protein. © 1994 Wiley‐Liss, Inc.