Structural evidence of genomic exon-deletion mediated by Alu-Alu recombination in a human case with heme oxygenase-1 deficiency.
We previously reported a family affected by heme oxygenase-1 (HO-1) deficiency [Yachie et al., 1999]. The proband was a compound heterozygote for a complete loss of exon 2 (the maternal allele) and a two-nucleotide deletion within exon 3 (the paternal allele). In this report, we describe a large genomic deletion (1730 bp) including entire exon 2 in this family as a specific mechanism generating exon-2 absence observed in the HO-1 mRNA. Analysis of the deletion junction demonstrated fusion of a 5' portion of Alu-Sx element with a 3' portion of Alu-Sq element. The junction contained sequences with high homology to the recombinogenic Alu "core" sequence. These structural features of the HO-1 gene suggest homologous recombination associated with Alu element. This study presents the initial characterization of the HO-1 gene defect causing a human case of HO-1 deficiency and provides the molecular basis for understanding this genetic disease.
Department of Pediatrics, School of Medicine, Faculty of Medicine, Kanazawa University, Japan. saikawa@ped.m.kanazawa-u.ac.jp
Y
Y
Saikawa
H
H
Kaneda
L
L
Yue
S
S
Shimura
T
T
Toma
Y
Y
Kasahara
A
A
Yachie
S
S
Koizumi
D000483:Alleles; D020087:Alu Elements / Q000235:genetics*; D002461:Cell Line, Transformed; D005091:Exons / Q000235:genetics*; D005260:Female; D006580:Genetic Carrier Screening; D006419:Heme Oxygenase (Decyclizing) / Q000172:deficiency* / Q000235:genetics*; D051547:Heme Oxygenase-1; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D011995:Recombination, Genetic / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1