Identification of a novel deletion in the ABCC6 gene leading to Pseudoxanthoma elasticum
Evelin Katona1, Charalampos Aslanidis, Eva Remenyik
1Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany.
Insights
Genetic deletions in the ABCC6 gene cause Pseudoxanthoma elasticum (PXE). This study identified two novel ABCC6 genomic deletions in a severe PXE case, suggesting deletions may be more common than previously thought.
Area of Science:
- Genetics
- Molecular Biology
- Medical Science
Background:
- Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder affecting skin, eyes, and cardiovascular system.
- Genetic defects in the ABCC6 transporter are the known cause of PXE.
Observation:
- This study investigated the genetic basis of a PXE patient with early onset and severe systemic manifestations.
- Genomic DNA from peripheral blood was analyzed using direct sequencing.
Findings:
- The patient was compound heterozygous for ABCC6 mutations, with both alleles having genomic deletions.
- A novel 4.68 kb deletion (exon 24-25) was found on one allele, and a known exon 23-29 deletion on the other.
- Deletion breakpoints were located within introns 23 and 25, originating in Alu-repeats.
Implications:
- Genomic deletions in ABCC6 may be a more frequent cause of PXE than previously recognized.
- Future genetic analyses for PXE should include screening for large genomic deletions in ABCC6.
- Understanding these mutations is crucial for diagnosing and potentially treating severe PXE cases.
Background:
Pseudoxanthoma elasticum (PXE) is an inherited systemic disorder, characterized by dermal, ocular and cardiovascular lesions. Genetic defects of the ABCC6 (MRP6) transporter are known to cause PXE.
Objectives:
The purpose of this study was to identify the genetic background of a PXE patient with a very early onset of the disease and severe systemic involvement.
Methods:
Direct sequencing of genomic DNA obtained from peripheral whole blood.
Results:
Our patient was found to be compound heterozygous with both ABCC6 alleles having genomic deletions. A novel exon 24-25 deletion was identified on one allele, while the frequently observed exon 23-29 deletion was found on the other allele. The novel deletion is 4.68 kb long and was shown to extend from intron 23 to 25. DNA-sequencing of a 2.03 kb fusion fragment revealed the deletion breakpoints within introns 23 and 25 originating in the middle of two Alu-repeats.
Conclusion:
In a patient with severe clinical symptoms, we found two genomic deletions in regions that might be important for function of the ABCC6 transporter. Genomic deletions in ABCC6 may occur more frequently in PXE patients than previously expected and future genetic analysis should focus on these mutations as well.
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