A mutation (IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic exon in an Alu-element in intron 8 of the human β-glucuronidase gene

Vervoort, Raf; Gitzelmann, R; Lissens, Willy; Liebaers, Inge

doi:10.1007/pl00008709

Cited by 52 publications

(41 citation statements)

References 38 publications

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“…3c), is quite curious since there are several recent studies in which pseudoexons were characterised as Alu or LINE elements (Knebelmann et al 1995;Meili et al 2009;Mitchell et al 1991;Pérez et al 2009;Vervoort et al 1998), as well as with recent estimates indicating that up to 5% of human alternative exons could be derived from Alu sequences (Sorek et al 2004;Tazi et al 2009;Wood et al 2007). With this in mind, we looked for Alu sequences within GNPTAB exons, but no repetitive sequences were found in any of them, indicating that exonization was not an evolutionary mechanism at the GNPTAB gene.…”

Section: Resultsmentioning

confidence: 96%

Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient

Coutinho¹,

Santos

Lacerda

et al. 2011

JIMD Reports

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Mucolipidosis type II a/b is a severe, autosomal recessive lysosomal storage disorder, caused by a defect in the GNPTAB gene that codes for the a/b subunits of the GlcNAc-phosphotransferase. To date, over 100 different mutations have been identified in MLII a/b patients, but no large deletions have been reported. Here we present the first case of a large homozygous intragenic GNPTAB gene deletion (c.3435-386_3602 + 343del897) encompassing exon 19, identified in a ML II a/b patient. Long-range PCR and sequencing methodologies were used to refine the characterization of this rearrangement, leading to the identification of a 21 bp repetitive motif in introns 18 and 19. Further analysis revealed that both the 5 0 and 3 0

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Section: Resultsmentioning

confidence: 96%

Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient

Coutinho¹,

Santos

Lacerda

et al. 2011

JIMD Reports

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“…Cryptic exons have been shown to be activated by intron mutations that either create or strengthen splice sites or create a branch site (Highsmith et al 1994;Chillon et al 1995;Wang et al 1997;Vervoort et al 1998;Ars et al 2000). In addition, an intracryptic exon deletion has been shown to cause erroneous splicing (Pagani et al 2002;Eng et al 2004).…”

Section: Discussionmentioning

confidence: 99%

A novel cryptic exon identified in the 3′ region of intron 2 of the human dystrophin gene

et al. 2005

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The dystrophin gene, which is mutated in Duchenne muscular dystrophy (DMD), is the largest known human gene and is characterized by the huge size of its introns. Intron 2, the second largest intron, is 170-kb long and has been shown to include a 140-bp cryptic exon (exon 2a) in its 5¢ region. The rest of this intron has no known function. In this study, we find that another cryptic exon, located in the 3¢ region of intron 2, is activated in a promoter-or tissue-specific manner. An unknown 98-bp insertion precisely between exons 2 and 3 was identified in one of the dystrophin mRNAs from lymphocytes of a DMD patient with a duplication of exon 2. This 98-bp sequence, located in the 3¢ region of intron 2, was found to possess a branch point, acceptor and donor splice-site consensus sequences, and an exonic splicing enhancer sequence, and thus is a novel exon, which we named ''exon 2b.'' In lymphocytes, exon 2b incorporation was detected in the muscle-specific, promoter-driven transcript. Five of 20 normal human tissue mRNAs, including cardiac and skeletal muscle mRNAs, were confirmed to contain a fragment extending from exon 1 to exon 2b by reverse transcription PCR amplification, indicating that exon 2b is activated in a tissue-specific manner. This provides a clue to a novel cause of dystrophinopathy.

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“…The other side of the coin is that single-base mutations may change an alternative into a constitutive splice site [31,32]. Pathologies such as the Alport [35] and the Sly syndromes [36] are known to be caused by mutations that result in constitutive inclusion of an Alu exon. More recently, it was even discovered that alternative inclusion of an Alu exon might lead to a genetic disease.…”

Section: Visions and Reflections (Minireview)mentioning

confidence: 99%

Useful ‘junk’: Alu RNAs in the human transcriptome

Häsler

Samuelsson

Strub

2007

Cell. Mol. Life Sci.

134

119

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Abstract. Alu elements are the most abundant repetitive elements in the human genome; they are amplified by retrotransposition to reach the present number of more than one million copies. Alu elements can be transcribed in two different ways, by two independent polymerases. Free Alu RNAs are transcribed by Pol III from their own promoter, while embedded Alu RNAs are transcribed by Pol II as part of protein-and non-protein-coding RNAs. Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in posttranscriptional regulation of gene expression, for example by affecting protein translation, alternative splicing and mRNA stability. These discoveries illustrate how a part of the junk DNA content of the human genome has been recruited to important functions in regulation of gene expression.

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A mutation (IVS8+0.6kbdelTC) creating a new donor splice site activates a cryptic exon in an Alu-element in intron 8 of the human β-glucuronidase gene

Cited by 52 publications

References 38 publications

Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient

Alu-Alu Recombination Underlying the First Large Genomic Deletion in GlcNAc-Phosphotransferase Alpha/Beta (GNPTAB) Gene in a MLII Alpha/Beta Patient

A novel cryptic exon identified in the 3′ region of intron 2 of the human dystrophin gene

Useful ‘junk’: Alu RNAs in the human transcriptome

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