Pseudoxanthoma elasticum: Mutations in the MRP6 gene encoding a transmembrane ATP-binding cassette (ABC) transporter
AUTOR(ES)
Ringpfeil, Franziska
FONTE
The National Academy of Sciences
RESUMO
Pseudoxanthoma elasticum (PXE), the prototypic heritable connective tissue disorder affecting the elastic structures in the body, manifests with cutaneous, ophthalmologic, and cardiovascular findings, with considerable morbidity and mortality. The molecular basis of PXE has remained unknown, but the disease locus has recently been mapped to an ≈500-kb interval on chromosome 16p13.1, without evidence for locus heterogeneity. In this study, we report pathogenetic mutations in MRP6, a member of the ABC transporter gene family, in eight kindreds with PXE. The mutation detection strategy consisted of heteroduplex scanning of coding sequences in the MRP6 gene, which were amplified by PCR by using genomic DNA as template, followed by direct nucleotide sequencing. A total of 13 mutant MRP6 alleles were disclosed in the eight probands with PXE. These genetic lesions consisted of either single base pair substitutions resulting in missense, nonsense, or splice site mutations, or large deletions resulting in allelic loss of the MRP6 locus. Examination of clinically unaffected family members in four multiplex families identified heterozygous carriers, consistent with an autosomal recessive inheritance pattern. Collectively, identification of mutations in the MRP6 gene provides the basis to examine the pathomechanisms of PXE and allows development of DNA-based carrier detection, prenatal testing, and preimplantation genetic diagnosis in families with a history of this disease.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=18548Documentos Relacionados
- Vanadate-catalyzed photocleavage of the signature motif of an ATP-binding cassette (ABC) transporter
- Uptake of the ATP-Binding Cassette (ABC) Transporter Ste6 into the Yeast Vacuole Is Blocked in the doa4 Mutant
- Mutations that alter the transmembrane signalling pathway in an ATP binding cassette (ABC) transporter.
- Expression of an ATP-binding cassette transporter-encoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae.
- AtMRP1 gene of Arabidopsis encodes a glutathione S-conjugate pump: Isolation and functional definition of a plant ATP-binding cassette transporter gene