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Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum.
O Le Saux1, Z Urban, C Tschuch
1Laboratory of Matrix Pathobiology, Pacific Biomedical Research Center, University of Hawai'i, Honolulu, Hawai'i, USA.
Nature Genetics
|June 3, 2000
Summary
Researchers identified the first mutations causing Pseudoxanthoma elasticum (PXE), a genetic disorder affecting skin, arteries, and eyes. These mutations are found in the ABCC6 gene, linked to multidrug resistance protein.
Area of Science:
- Genetics
- Molecular Biology
- Ophthalmology
Background:
- Pseudoxanthoma elasticum (PXE) is a rare genetic disorder causing calcification of elastic fibers in the skin, arteries, and retina.
- PXE leads to dermal lesions, arterial insufficiency, and retinal hemorrhages, potentially causing vision loss.
- Both sporadic and familial forms (autosomal recessive and dominant) of PXE are known, with variable expressivity.
Purpose of the Study:
- To identify the genetic cause of Pseudoxanthoma elasticum (PXE).
- To refine the chromosomal locus associated with PXE and pinpoint causative genes.
Main Methods:
- Genetic linkage analysis was used to narrow down the PXE locus on chromosome 16p13.1 to an 820-kb region.
- Candidate genes within this refined region were analyzed for mutations.
- Exclusion of five candidate genes and identification of mutations in the ABCC6 gene.
Main Results:
- Mutations in the ABCC6 gene were identified as the cause of Pseudoxanthoma elasticum (PXE).
- The ABCC6 gene encodes a protein associated with multidrug resistance.
- Exclusion of five other candidate genes within the 16p13.1 locus.
Conclusions:
- The ABCC6 gene is the first identified gene responsible for Pseudoxanthoma elasticum (PXE).
- These findings provide a molecular basis for understanding PXE pathogenesis.
- Future research can focus on the role of ABCC6 in elastic tissue calcification and develop targeted therapies.