Identification of Alu-mediated, large deletion-spanning exons 2–4 in a patient with mitochondrial acetoacetyl-CoA thiolase deficiency

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 here...

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Veröffentlicht in:Molecular genetics and metabolism 2006-11, Vol.89 (3), p.222-226
Hauptverfasser: Zhang, Gaixiu, Fukao, Toshiyuki, Sakurai, Satomi, Yamada, Keitaro, Michael Gibson, K., Kondo, Naomi
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Sprache:eng
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Zusammenfassung: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 6.4 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.
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2006.06.010