title: Copy number variation in the ATP-binding cassette transporter ABCC6 gene and ABCC6 pseudogenes in patients with pseudoxanthoma elasticum.
abstract: Single mutations in the ATP-binding cassette transporter (ABCC6) gene (OMIM 603234) are known to cause the rare autosomal recessive disease pseudoxanthoma elasticum (PXE). Recently, we have found that copy number variations (CNVs) in pseudogenes of the ABCC6 gene are quite common. The aim of this study was to investigate the frequency and possible contribution of CNV in ABCC6 and its pseudogenes in PXE. Genomic DNA from 212 PXE individuals were examined for copy number by pyrosequencing and quantitative polymerase chain reaction (PCR) and compared with healthy individuals. The frequency of PXE individuals with any CNV was higher than in healthy individuals. The majority of variation comprised known and possibly new deletions in the ABCC6 gene and duplications of the ABCC6P1 and ABCC6P2 genes. ABCC6 deletions and ABCC6P2 duplications were not observed in 142 healthy individuals. In conclusion, by pyrosequencing and quantitative PCR, we were able to detect known and possibly new deletions in the ABCC6 gene that may have caused the PXE phenotype. Pyrosequencing may be used in PXE patients who have obtained incomplete genotype from conventional techniques. The frequency of ABCC6P2 pseudogene duplication was more common in PXE patients than healthy individuals and may affect the PXE phenotype.
authors.affiliation: Department of Pharmacology, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Marianne K
authors.initials: MK
authors.lastname: Kringen
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Stormo
authors.affiliation: Department of Medical Biochemistry, Oslo University Hospital Ullevål, Oslo, Norway ; Department of Medical Biochemistry, Institute of Clinical Medicine, University of Oslo Oslo, Norway.
authors.forename: Jens Petter
authors.initials: JP
authors.lastname: Berg
authors.affiliation: PXE International, Genetic Alliance Washington, DC.
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Terry
authors.affiliation: PXE International, Genetic Alliance Washington, DC.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Vocke
authors.affiliation: PXE International, Genetic Alliance Washington, DC.
authors.forename: Samar
authors.initials: S
authors.lastname: Rizvi
authors.affiliation: Herz- und Diabeteszentrum NRW, Institut für Laboratoriums- und Transfusionsmedizin, Universitätsklinik der Ruhr-Universität Bochum Bad Oeynhausen, Germany.
authors.forename: Doris
authors.initials: D
authors.lastname: Hendig
authors.affiliation: Furst Medical Laboratory Oslo, Norway.
authors.forename: Armin P
authors.initials: AP
authors.lastname: Piehler
keywords: ABCC6; copy number variation; pseudogenes; pseudoxanthoma elasticum