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Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region

(2010) JOURNAL OF HUMAN GENETICS. 55(2). p.112-117
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Abstract
Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, >200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 2010
Keywords
ABCC6, genomic instability, MUTATIONS, GENE, MLPA/molecular analysis, pseudoxanthoma elasticum, TRANSPORTER, PHENOTYPE, DISEASE, UPDATE

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Chicago
Costrop, Laura, Olivier Vanakker, Lut Van Laer, Olivier Le Saux, L Martin, N Chassaing, D Guerra, I Pasquali-Ronchetti, Paul Coucke, and Anne De Paepe. 2010. “Novel Deletions Causing Pseudoxanthoma Elasticum Underscore the Genomic Instability of the ABCC6 Region.” Journal of Human Genetics 55 (2): 112–117.
APA
Costrop, L., Vanakker, O., Van Laer, L., Le Saux, O., Martin, L., Chassaing, N., Guerra, D., et al. (2010). Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region. JOURNAL OF HUMAN GENETICS, 55(2), 112–117.
Vancouver
1.
Costrop L, Vanakker O, Van Laer L, Le Saux O, Martin L, Chassaing N, et al. Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region. JOURNAL OF HUMAN GENETICS. NEW YORK: NATURE PUBLISHING GROUP; 2010;55(2):112–7.
MLA
Costrop, Laura, Olivier Vanakker, Lut Van Laer, et al. “Novel Deletions Causing Pseudoxanthoma Elasticum Underscore the Genomic Instability of the ABCC6 Region.” JOURNAL OF HUMAN GENETICS 55.2 (2010): 112–117. Print.
@article{1013943,
  abstract     = {Mutations in ABCC6 cause pseudoxanthoma elasticum (PXE), a heritable disease that affects elastic fibers. Thus far, {\textrangle}200 mutations have been characterized by various PCR-based techniques (primarily direct sequencing), identifying up to 90\% of PXE-causing alleles. This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. To detect ABCC6 deletions/insertions, which can be missed by direct sequencing, multiplex ligation-dependent probe amplification (MLPA) was applied in PXE patients with an incomplete genotype. MLPA was performed in 35 PXE patients with at least one unidentified mutant allele after exonic sequencing and exclusion of the recurrent exon 23-29 deletion. Six multi-exon deletions and four single-exon deletions were detected. Using MLPA in addition to sequencing, we expanded the ABCC6 mutation spectrum with 9 novel deletions and characterized 25\% of unidentified disease alleles. Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. Journal of Human Genetics (2010) 55, 112-117; doi: 10.1038/jhg.2009.132; published online 15 January 2010},
  author       = {Costrop, Laura and Vanakker, Olivier and Van Laer, Lut and Le Saux, Olivier and Martin, L and Chassaing, N and Guerra, D and Pasquali-Ronchetti, I and Coucke, Paul and De Paepe, Anne},
  issn         = {1434-5161},
  journal      = {JOURNAL OF HUMAN GENETICS},
  keyword      = {ABCC6,genomic instability,MUTATIONS,GENE,MLPA/molecular analysis,pseudoxanthoma elasticum,TRANSPORTER,PHENOTYPE,DISEASE,UPDATE},
  language     = {eng},
  number       = {2},
  pages        = {112--117},
  publisher    = {NATURE PUBLISHING GROUP},
  title        = {Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region},
  url          = {http://dx.doi.org/10.1038/jhg.2009.132},
  volume       = {55},
  year         = {2010},
}

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