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A novel single-base substitution (c.1124A>G) that activates a 5-base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl-CoA thiolase gene.
Mol Genet Metab 2008; 94(4):417-21MG

Abstract

Most mutations related to aberrant splicing occur in conserved splice acceptor and donor sites. Some exonic mutations also affect splicing. We identified and characterized a point mutation (c.1124A>G) in an Australian patient (GK43) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK43 is a homozygote of c.1124A>G, which activates a cryptic splice donor site 5 bases upstream from c.1124A>G within exon 11, causing aberrant splicing in most transcripts. The aberrant splicing results in c.1120-1163 (44-base) deletion, causing a frameshift in T2 mRNA. A mini-gene splicing experiment confirmed that the c.1124A>G substitution was responsible for this aberrant splicing. This cryptic splice site has a Shapiro and Senapathy score (70.0) in a normal sequence but if mutated, the score (84.3) becomes higher than the one in the authentic splice donor site of intron 11 (81.4). This is an example in which a point mutation activates a cryptic splice donor site motif that is used preferentially over a downstream authentic splice site.

Authors+Show Affiliations

Department of Pediatrics, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. address: toshi-gif@umim.netNo 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

18511318

Citation

Fukao, Toshiyuki, et al. "A Novel Single-base Substitution (c.1124A>G) That Activates a 5-base Upstream Cryptic Splice Donor Site Within Exon 11 in the Human Mitochondrial acetoacetyl-CoA Thiolase Gene." Molecular Genetics and Metabolism, vol. 94, no. 4, 2008, pp. 417-21.
Fukao T, Boneh A, Aoki Y, et al. A novel single-base substitution (c.1124A>G) that activates a 5-base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl-CoA thiolase gene. Mol Genet Metab. 2008;94(4):417-21.
Fukao, T., Boneh, A., Aoki, Y., & Kondo, N. (2008). A novel single-base substitution (c.1124A>G) that activates a 5-base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl-CoA thiolase gene. Molecular Genetics and Metabolism, 94(4), pp. 417-21. doi:10.1016/j.ymgme.2008.04.014.
Fukao T, et al. A Novel Single-base Substitution (c.1124A>G) That Activates a 5-base Upstream Cryptic Splice Donor Site Within Exon 11 in the Human Mitochondrial acetoacetyl-CoA Thiolase Gene. Mol Genet Metab. 2008;94(4):417-21. PubMed PMID: 18511318.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel single-base substitution (c.1124A>G) that activates a 5-base upstream cryptic splice donor site within exon 11 in the human mitochondrial acetoacetyl-CoA thiolase gene. AU - Fukao,Toshiyuki, AU - Boneh,Avihu, AU - Aoki,Yusuke, AU - Kondo,Naomi, Y1 - 2008/06/03/ PY - 2008/02/26/received PY - 2008/04/17/revised PY - 2008/04/17/accepted PY - 2008/5/31/pubmed PY - 2008/8/15/medline PY - 2008/5/31/entrez SP - 417 EP - 21 JF - Molecular genetics and metabolism JO - Mol. Genet. Metab. VL - 94 IS - 4 N2 - Most mutations related to aberrant splicing occur in conserved splice acceptor and donor sites. Some exonic mutations also affect splicing. We identified and characterized a point mutation (c.1124A>G) in an Australian patient (GK43) with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. GK43 is a homozygote of c.1124A>G, which activates a cryptic splice donor site 5 bases upstream from c.1124A>G within exon 11, causing aberrant splicing in most transcripts. The aberrant splicing results in c.1120-1163 (44-base) deletion, causing a frameshift in T2 mRNA. A mini-gene splicing experiment confirmed that the c.1124A>G substitution was responsible for this aberrant splicing. This cryptic splice site has a Shapiro and Senapathy score (70.0) in a normal sequence but if mutated, the score (84.3) becomes higher than the one in the authentic splice donor site of intron 11 (81.4). This is an example in which a point mutation activates a cryptic splice donor site motif that is used preferentially over a downstream authentic splice site. SN - 1096-7206 UR - https://www.unboundmedicine.com/medline/citation/18511318/A_novel_single_base_substitution__c_1124A>G__that_activates_a_5_base_upstream_cryptic_splice_donor_site_within_exon_11_in_the_human_mitochondrial_acetoacetyl_CoA_thiolase_gene_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1096-7192(08)00122-4 DB - PRIME DP - Unbound Medicine ER -