ClinVar

Fukao et al. (1994) reported a Caucasian girl, born to nonconsanguineous parents, in whom the diagnosis of 3-ketothiolase deficiency (203750) was made when she was 3 years old and after multiple ketoacidotic attacks. Her growth and development were normal, and there was no mental retardation. She was found to be a compound heterozygote; the maternal allele had a 1136G-to-T transversion, resulting in a gly379-to-val substitution (G379V) in the thiolase precursor. Cells transfected with cDNA carrying the G379V mutation showed no evidence of restored T2 activity. The paternal allele was associated with exon 8 skipping at the cDNA level. In the paternal allele at the gene level, a C-to-T transition causing a gln272-to-ter (Q272X) change was identified within exon 8, 13 bp from the 5-prime splice site of intron 8. Splicing experiments showed that the exonic mutation caused partial skipping of exon 8. This substitution was thought to alter the secondary structure of T2 pre-mRNA around exon 8 and thus impede normal splicing. They cited a similar situation reported by Steingrimsdottir et al. (1992), who detected aberrant splicing in the HGPRT (308000) gene resulting from a mutation located 13 nucleotides from the 5-prime splice site of intron 8 and causing exon 8 skipping in 90% of HGPRT transcripts.