RGD Reference Report - Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Mutation detection in the ABCC6 gene and genotype-phenotype analysis in a large international case series affected by pseudoxanthoma elasticum.

Authors: Pfendner, EG  Vanakker, OM  Terry, SF  Vourthis, S  McAndrew, PE  McClain, MR  Fratta, S  Marais, AS  Hariri, S  Coucke, PJ  Ramsay, M  Viljoen, D  Terry, PF  De Paepe, A  Uitto, J  Bercovitch, LG 
Citation: Pfendner EG, etal., J Med Genet. 2007 Oct;44(10):621-8. Epub 2007 Jul 6.
RGD ID: 11038781
Pubmed: PMID:17617515   (View Abstract at PubMed)
PMCID: PMC2597973   (View Article at PubMed Central)
DOI: DOI:10.1136/jmg.2007.051094   (Journal Full-text)

BACKGROUND: Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder with considerable phenotypic variability, mainly affects the eyes, skin and cardiovascular system, characterised by dystrophic mineralization of connective tissues. It is caused by mutations in the ABCC6 (ATP binding cassette family C member 6) gene, which encodes MRP6 (multidrug resistance-associated protein 6). OBJECTIVE: To investigate the mutation spectrum of ABCC6 and possible genotype-phenotype correlations. METHODS: Mutation data were collected on an international case series of 270 patients with PXE (239 probands, 31 affected family members). A denaturing high-performance liquid chromatography-based assay was developed to screen for mutations in all 31 exons, eliminating pseudogene coamplification. In 134 patients with a known phenotype and both mutations identified, genotype-phenotype correlations were assessed. RESULTS: In total, 316 mutant alleles in ABCC6, including 39 novel mutations, were identified in 239 probands. Mutations were found to cluster in exons 24 and 28, corresponding to the second nucleotide-binding fold and the last intracellular domain of the protein. Together with the recurrent R1141X and del23-29 mutations, these mutations accounted for 71.5% of the total individual mutations identified. Genotype-phenotype analysis failed to reveal a significant correlation between the types of mutations identified or their predicted effect on the expression of the protein and the age of onset and severity of the disease. CONCLUSIONS: This study emphasises the principal role of ABCC6 mutations in the pathogenesis of PXE, but the reasons for phenotypic variability remain to be explored.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
pseudoxanthoma elasticum  IAGP 11038781DNA:mutations:exon and intron:multipleRGD 
pseudoxanthoma elasticum  ISOABCC6 (Homo sapiens)11038781; 11038781DNA:mutations:exon and intron:multipleRGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal cutaneous elastic fiber morphology  IAGP 11038781DNA:mutations:exon and intron:multipleRGD 
Abnormal fundus morphology  IAGP 11038781DNA:mutations:exon and intron:multipleRGD 
Localized skin lesion  IAGP 11038781DNA:mutations:exon and intron:multipleRGD 
Objects Annotated

Genes (Rattus norvegicus)
Abcc6  (ATP binding cassette subfamily C member 6)

Genes (Mus musculus)
Abcc6  (ATP-binding cassette, sub-family C member 6)

Genes (Homo sapiens)
ABCC6  (ATP binding cassette subfamily C member 6)


Additional Information