title: Identification of Alu-mediated, large deletion-spanning exons 2-4 in a patient with mitochondrial acetoacetyl-CoA thiolase deficiency.
abstract: Mitochondrial acetoacetyl-CoA thiolase (T2) deficiency is a rare inherited metabolic disorder affecting isoleucine catabolism and ketone body metabolism. So far, more than 39 different mutations have been identified in 60 T2-deficient patients. However, no large deletions have been reported. We herein report the first case of a large T2 gene deletion from intron 1 to intron 4 in a T2-deficient patient (GK41). cDNA analysis revealed that an aberrant cDNA with exons 2-5 skipping was a major transcript, associated with a minor transcript of exons 2-4 skipping with a 94-bp insertion composed of an intron 1 sequence. Genomic analysis indicated an absence of PCR amplification of exons 2-4 and gene deletion was revealed by Southern blot analysis. Cloning and sequencing long range PCR products revealed a 6.4kb deletion. Alu element-mediated unequal homologous recombination between an Alu-Sx in intron 1 and another Alu-Y in intron 4 appears to be responsible for this deletion.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Gifu 501-1194, Japan.
authors.forename: Gaixiu
authors.initials: G
authors.lastname: Zhang
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Fukao
authors.forename: Satomi
authors.initials: S
authors.lastname: Sakurai
authors.forename: Keitaro
authors.initials: K
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Michael Gibson
authors.forename: Naomi
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000172:deficiency*; D020087:Alu Elements / Q000235:genetics*; D001483:Base Sequence; D015139:Blotting, Southern; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000235:genetics; D005091:Exons / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017384:Sequence Deletion / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D000101:Acetyl-CoA C-Acetyltransferase