title: Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY.
abstract: Mutation-induced activation of splice sites in intronic repetitive sequences has contributed significantly to the evolution of exon-intron structure and genetic disease. Such events have been associated with mutations within transposable elements, most frequently in mutation hot-spots of Alus. Here, we report a case of Alu exonization resulting from a 367-nt genomic COL4A5 deletion that did not encompass any recognizable transposed element, leading to the Alport syndrome. The deletion brought to proximity the 5' splice site of COL4A5 exon 33 and a cryptic 3' splice site in an antisense AluY copy in intron 32. The fusion exon was depleted of purines and purine-rich splicing enhancers, but had low levels of intramolecular secondary structure, was flanked by short introns and had strong 5' and Alu-derived 3' splice sites, apparently compensating poor composition and context of the new exon. This case demonstrates that Alu splice sites can be activated by outlying deletions, highlighting Alu versatility in shaping the exon-intron organization and expanding the spectrum of mutational mechanisms that introduce repetitive sequences in mRNAs.
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Kandai
authors.initials: K
authors.lastname: Nozu
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Kazumoto
authors.initials: K
authors.lastname: Iijima
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Saga University Saga, Japan.
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Ohtsuka
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Xue Jun
authors.initials: XJ
authors.lastname: Fu
authors.affiliation: Department of Pediatrics, Kobe University Graduate School of Medicine Kobe, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaito
authors.affiliation: Department of Pediatrics, Wakayama Medical University Wakayama, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakanishi
authors.affiliation: Faculty of Medicine, University of Southampton Southampton, U.K.
authors.forename: Igor
authors.initials: I
authors.lastname: Vorechovsky
keywords: Alu; RNA processing; collagen; exonization; intron