title: ABCC6 mutations in pseudoxanthoma elasticum: an update including eight novel ones.
abstract: OBJECTIVE
  Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of connective tissue, affecting the retina, the skin, and the cardiovascular system. PXE is caused by mutations in ABCC6. Up to now, the literature reports that there are 180 different ABCC6 mutations in PXE. The purpose of this paper is to report eight novel mutations in ABCC6 and to update the spectrum and frequency of ABCC6 mutations in PXE patients.
  
  
  METHODS
  Eye, skin, and DNA examinations were performed using standard methodologies. We newly investigated the gene in 90 probands by denaturing high-performance liquid chromatography (dHPLC) and direct sequencing. We examined a total of 166 probands.
  
  
  RESULTS
  Eight novel ABCC6 mutations (c.1685T>C, p.Met562Thr; c.2477T>C, p.Leu826Pro; c.2891G>C, p.Arg964Pro; c.3207C>A, p.Tyr1069X; c.3364delT, p.Ser1122fs; c.3717T>G, p.Tyr1293X; c.3871G>A, p.Ala1291Thr; c.4306_4312del, p.Thr1436fs) were found in seven unrelated patients. Currently, our mutation detection score is at least one ABCC6 mutation in 87% of patients with a clinical diagnosis of PXE.
  
  
  CONCLUSIONS
  Our results support that ABCC6 is the most important, and probably the only, causative gene of PXE. In total, 188 different ABCC6 mutations have now been reported in PXE in the literature.
authors.affiliation: Department of Clinical and Molecular Ophthalmogenetics, Netherlands Institute for Neuroscience, an institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.
authors.forename: Astrid S
authors.initials: AS
authors.lastname: Plomp
authors.forename: Ralph J
authors.initials: RJ
authors.lastname: Florijn
authors.forename: Jacoline
authors.initials: J
authors.lastname: Ten Brink
authors.forename: Bruce
authors.initials: B
authors.lastname: Castle
authors.forename: Helen
authors.initials: H
authors.lastname: Kingston
authors.forename: Ana
authors.initials: A
authors.lastname: Martín-Santiago
authors.forename: Theo G M F
authors.initials: TG
authors.lastname: Gorgels
authors.forename: Paulus T V M
authors.initials: PT
authors.lastname: de Jong
authors.forename: Arthur A B
authors.initials: AA
authors.lastname: Bergen
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D017124:Conserved Sequence; D005260:Female; D017353:Gene Deletion; D006801:Humans; D008297:Male; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D009154:Mutation; D020125:Mutation, Missense; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000473:pathology; D012160:Retina / Q000473:pathology; D012867:Skin / Q000473:pathology
chemical_list: D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human