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Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A thiolase deficiency.
J Clin Invest 1994; 93(3):1035-41JCI

Abstract

We identified a novel exonic mutation which causes exon skipping in the mitochondrial acetoacetyl-CoA thiolase (T2) gene from a girl with T2 deficiency (GK07). GK07 is a compound heterozygote; the maternal allele has a novel G to T transversion at position 1136 causing Gly379 to Val substitution (G379V) of the T2 precursor. In case of in vivo expression analysis, cells transfected with this mutant cDNA showed no evidence of restored T2 activity. The paternal allele was associated with exon 8 skipping at the cDNA level. At the gene level, a C to T transition causing Gln272 to termination codon (Q272STOP) was identified within exon 8, 13 bp from the 5' splice site of intron 8 in the paternal allele. The mRNA with Q272STOP could not be detected in GK07 fibroblasts, presumably because pre-mRNA with Q272STOP was unstable because of the premature termination. In vivo splicing experiments revealed 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. The role of exon sequences in the splicing mechanism is indicated by the exon skipping which occurred with an exonic mutation.

Authors+Show Affiliations

Department of Pediatrics, Gifu University School of Medicine, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7907600

Citation

Fukao, T, et al. "Identification of a Novel Exonic Mutation at -13 From 5' Splice Site Causing Exon Skipping in a Girl With Mitochondrial Acetoacetyl-coenzyme a Thiolase Deficiency." The Journal of Clinical Investigation, vol. 93, no. 3, 1994, pp. 1035-41.
Fukao T, Yamaguchi S, Wakazono A, et al. Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A thiolase deficiency. J Clin Invest. 1994;93(3):1035-41.
Fukao, T., Yamaguchi, S., Wakazono, A., Orii, T., Hoganson, G., & Hashimoto, T. (1994). Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A thiolase deficiency. The Journal of Clinical Investigation, 93(3), pp. 1035-41.
Fukao T, et al. Identification of a Novel Exonic Mutation at -13 From 5' Splice Site Causing Exon Skipping in a Girl With Mitochondrial Acetoacetyl-coenzyme a Thiolase Deficiency. J Clin Invest. 1994;93(3):1035-41. PubMed PMID: 7907600.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of a novel exonic mutation at -13 from 5' splice site causing exon skipping in a girl with mitochondrial acetoacetyl-coenzyme A thiolase deficiency. AU - Fukao,T, AU - Yamaguchi,S, AU - Wakazono,A, AU - Orii,T, AU - Hoganson,G, AU - Hashimoto,T, PY - 1994/3/1/pubmed PY - 1994/3/1/medline PY - 1994/3/1/entrez SP - 1035 EP - 41 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 93 IS - 3 N2 - We identified a novel exonic mutation which causes exon skipping in the mitochondrial acetoacetyl-CoA thiolase (T2) gene from a girl with T2 deficiency (GK07). GK07 is a compound heterozygote; the maternal allele has a novel G to T transversion at position 1136 causing Gly379 to Val substitution (G379V) of the T2 precursor. In case of in vivo expression analysis, cells transfected with this mutant cDNA showed no evidence of restored T2 activity. The paternal allele was associated with exon 8 skipping at the cDNA level. At the gene level, a C to T transition causing Gln272 to termination codon (Q272STOP) was identified within exon 8, 13 bp from the 5' splice site of intron 8 in the paternal allele. The mRNA with Q272STOP could not be detected in GK07 fibroblasts, presumably because pre-mRNA with Q272STOP was unstable because of the premature termination. In vivo splicing experiments revealed 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. The role of exon sequences in the splicing mechanism is indicated by the exon skipping which occurred with an exonic mutation. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/7907600/Identification_of_a_novel_exonic_mutation_at__13_from_5'_splice_site_causing_exon_skipping_in_a_girl_with_mitochondrial_acetoacetyl_coenzyme_A_thiolase_deficiency_ L2 - https://doi.org/10.1172/JCI117052 DB - PRIME DP - Unbound Medicine ER -