title: Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region.
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.
authors.affiliation: Center for Medical Genetics, Ghent University, Belgium.
authors.forename: Laura M F
authors.initials: LM
authors.lastname: Costrop
authors.forename: Olivier O M
authors.initials: OO
authors.lastname: Vanakker
authors.forename: Lut
authors.initials: L
authors.lastname: Van Laer
authors.forename: Olivier
authors.initials: O
authors.lastname: Le Saux
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Deanna
authors.initials: D
authors.lastname: Guerra
authors.forename: Ivonne
authors.initials: I
authors.lastname: Pasquali-Ronchetti
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Coucke
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
mesh_terms: D055028:Comparative Genomic Hybridization; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D042822:Genomic Instability / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D021141:Nucleic Acid Amplification Techniques; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human