INVESTIGADORES
CASALE Cesar Horacio
artículos
Título:
A nonsense mutation in the 3-hydrixy-3-methylglutaryl coenzime A lyase (HL) gene produce exon skipping in two patients of different origin with HL deficiency
Autor/es:
PIE J; CASALS N; CASALE CH; BUESA C; MASCARO C; BARCELO A; ZABOT T; EYKENS, F.; DIVRY, P; HEGARDT FG
Revista:
BIOCHEMICAL JOURNAL
Referencias:
Año: 1997 vol. 323 p. 329 - 335
ISSN:
0264-6021
Resumen:
A novel nonsense mutation associated with the skipping of
constitutive exon 2 of the 3-hydroxy-3-methylglutaryl-CoA
lyase gene was found in two patients, from Portugal and
Morocco, with 3-hydroxy-3-methylglutaric acidemia. By reverse
transcriptase PCR and single-strand conformational polymorphism
a G±T transversion was located, at nucleotide 109,
of the 3-hydroxy-3-methylglutaryl-CoA lyase cDNA, within
exon 2. Two mRNAs were produced as a result of this nonsense
mutation: one of the expected size that contains the premature
stop codon UAA, and the other with a deletion of 84 bp
corresponding to the whole of exon 2. This deletion produced the
loss of the last seven amino acids of the leader peptide and the
®rst 21 amino acids of the mature protein. The nonsense mutation
was found in a purine-rich GGAAG sequence, which is equal to,
or similar to, others reported to be exonic splicing enhancers
(ESE). We suggest that the nonsense mutation may affect a
possible ESE on exon 2, which would hinder the splice site
selection and facilitate an aberrant splice with the skipping of
this exon. Determination by quantitative PCR shows that the
ratio of mRNA with the nonsense mutation to the mRNA with
the deletion is approx. 3: 1.