Alport syndrome caused by a COL4A5 deletion and exonization of an adjacent AluY. Issue 5 (28th May 2014)

• Record Type: Journal Article
• Authors: Nozu, Kandai; Iijima, Kazumoto; Ohtsuka, Yasufumi; Fu, Xue Jun; Kaito, Hiroshi; Nakanishi, Koichi; Vorechovsky, Igor
• Is Part Of: Molecular genetics & genomic medicine. Volume 2:Issue 5(2014:Sep.)
• Page Start: 451
• Page End: 453
• Publication Date: 2014-05-28
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.89
• Languages: English
• ISSNs: 2324-9269

Abstract

<abstract abstract-type="main" id="mgg389-abs-0001"> <title>Abstract</title> <p>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 <italic>Alu</italic>s. Here, we report a case of <italic>Alu</italic> exonization resulting from a 367‐nt genomic <italic>COL4A5</italic> deletion that did not encompass any recognizable transposed element, leading to the Alport syndrome. The deletion brought to proximity the 5′ splice site of <italic>COL4A5</italic> exon 33 and a cryptic 3′ splice site in an antisense <italic>AluY</italic> 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 <italic>Alu</italic>‐derived 3′ splice sites, apparently compensating poor composition and context of the new exon. This case demonstrates that <italic>Alu</italic> splice sites can be activated by outlying deletions, highlighting <italic>Alu</italic> versatility in shaping the exon–intron organization and expanding the spectrum of mutational mechanisms that introduce repetitive sequences in mRNAs.</p> </abstract>