Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1999824 | Molecular Genetics and Metabolism | 2006 | 5 Pages |
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 6.4Â kb 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.
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Authors
Gaixiu Zhang, Toshiyuki Fukao, Satomi Sakurai, Keitaro Yamada, K. Michael Gibson, Naomi Kondo,