title: Identification of a novel deletion in the ABCC6 gene leading to Pseudoxanthoma elasticum.
abstract: BACKGROUND
  Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder, characterized by dermal, ocular and cardiovascular lesions. Genetic defects of the ABCC6 (MRP6) transporter are known to cause PXE.
  
  
  OBJECTIVE
  The purpose of this study was to identify the genetic background of a PXE patient with a very early onset of the disease and severe systemic involvement.
  
  
  METHODS
  Direct sequencing of genomic DNA obtained from peripheral whole blood.
  
  
  RESULTS
  Our patient was found to be compound heterozygous with both ABCC6 alleles having genomic deletions. A novel exon 24-25 deletion was identified on one allele, while the frequently observed exon 23-29 deletion was found on the other allele. The novel deletion is 4.68 kb long and was shown to extend from intron 23 to 25. DNA-sequencing of a 2.03 kb fusion fragment revealed the deletion breakpoints within introns 23 and 25 originating in the middle of two Alu-repeats.
  
  
  CONCLUSIONS
  In a patient with severe clinical symptoms, we found two genomic deletions in regions that might be important for function of the ABCC6 transporter. Genomic deletions in ABCC6 may occur more frequently in PXE patients than previously expected and future genetic analysis should focus on these mutations as well.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
authors.forename: Evelin
authors.initials: E
authors.lastname: Katona
authors.forename: Charalampos
authors.initials: C
authors.lastname: Aslanidis
authors.forename: Eva
authors.initials: E
authors.lastname: Remenyik
authors.forename: Márta
authors.initials: M
authors.lastname: Csikós
authors.forename: Sarolta
authors.initials: S
authors.lastname: Kárpáti
authors.forename: György
authors.initials: G
authors.lastname: Paragh
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D006801:Humans; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D011561:Pseudoxanthoma Elasticum / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human