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Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2

BACKGROUND: The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is ca...

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Autores principales: Bernard, Veronica, Minnerop, Martina, Bürk, Katrin, Kreuz, Friedmar, Gillessen-Kaesbach, Gabriele, Zühlke, Christine
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749023/
https://www.ncbi.nlm.nih.gov/pubmed/19744353
http://dx.doi.org/10.1186/1471-2350-10-87
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author Bernard, Veronica
Minnerop, Martina
Bürk, Katrin
Kreuz, Friedmar
Gillessen-Kaesbach, Gabriele
Zühlke, Christine
author_facet Bernard, Veronica
Minnerop, Martina
Bürk, Katrin
Kreuz, Friedmar
Gillessen-Kaesbach, Gabriele
Zühlke, Christine
author_sort Bernard, Veronica
collection PubMed
description BACKGROUND: The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (SETX). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions. METHODS: To detect mutations in patients showing a clinical phenotype consistent with AOA2, the coding region including splice sites of the SETX gene was sequenced and dosage analyses for all exons were performed on genomic DNA. The sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was determined. RESULTS: Sequence analyses of the SETX gene in four patients revealed a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1) and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15. This deletion was present in a homozygous state in patient P4. CONCLUSION: Our findings indicate that gross mutations seem to be a frequent cause of AOA2 and reveal the importance of additional copy number analysis for routine diagnostics.
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spelling pubmed-27490232009-09-23 Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2 Bernard, Veronica Minnerop, Martina Bürk, Katrin Kreuz, Friedmar Gillessen-Kaesbach, Gabriele Zühlke, Christine BMC Med Genet Research Article BACKGROUND: The autosomal recessively inherited ataxia with oculomotor apraxia 2 (AOA2) is a neurodegenerative disorder characterized by juvenile or adolescent age of onset, gait ataxia, cerebellar atrophy, axonal sensorimotor neuropathy, oculomotor apraxia, and elevated serum AFP levels. AOA2 is caused by mutations within the senataxin gene (SETX). The majority of known mutations are nonsense, missense, and splice site mutations, as well as small deletions and insertions. METHODS: To detect mutations in patients showing a clinical phenotype consistent with AOA2, the coding region including splice sites of the SETX gene was sequenced and dosage analyses for all exons were performed on genomic DNA. The sequence of cDNA fragments of alternative transcripts isolated after RT-PCR was determined. RESULTS: Sequence analyses of the SETX gene in four patients revealed a heterozygous nonsense mutation or a 4 bp deletion in three cases. In another patient, PCR amplification of exon 11 to 15 dropped out. Dosage analyses and breakpoint localisation yielded a 1.3 kb LINE1 insertion in exon 12 (patient P1) and a 6.1 kb deletion between intron 11 and intron 14 (patient P2) in addition to the heterozygous nonsense mutation R1606X. Patient P3 was compound heterozygous for a 4 bp deletion in exon 10 and a 20.7 kb deletion between intron 10 and 15. This deletion was present in a homozygous state in patient P4. CONCLUSION: Our findings indicate that gross mutations seem to be a frequent cause of AOA2 and reveal the importance of additional copy number analysis for routine diagnostics. BioMed Central 2009-09-11 /pmc/articles/PMC2749023/ /pubmed/19744353 http://dx.doi.org/10.1186/1471-2350-10-87 Text en Copyright © 2009 Bernard et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Bernard, Veronica
Minnerop, Martina
Bürk, Katrin
Kreuz, Friedmar
Gillessen-Kaesbach, Gabriele
Zühlke, Christine
Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
title Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
title_full Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
title_fullStr Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
title_full_unstemmed Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
title_short Exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
title_sort exon deletions and intragenic insertions are not rare in ataxia with oculomotor apraxia 2
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749023/
https://www.ncbi.nlm.nih.gov/pubmed/19744353
http://dx.doi.org/10.1186/1471-2350-10-87
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