Background Pseudoxanthoma elasticum (PXE) is a genetic metabolic disease with autosomal recessive inheritance caused by mutations in the ABCC6gene. The lack of functional ABCC6 protein leads to ectopic mineralization that is most apparent in the elastic tissues of the skin, eyes and blood vessels.
Objective For the advancement in research on rare genetic diseases.
Discussion Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder of ectopic mineralization and fragmentation of elastic fibers in skin, eyes, cardiovascular and digestive system. PXE is caused by sequence variants in ABCC6, which encodes multidrug resistance-associated protein 6 (MRP6, also known as the ABCC6 protein). MRP6 is an important regulator of inorganic plasma pyrophosphate that acts as an inhibitor of ectopic mineralization observed in PXE patients with low inorganic plasma pyrophosphate levels. The current study was designed to investigate underlying genetic defect in two unrelated Pakistani families affected with PXE. Whole exome sequencing followed by Sanger sequencing was performed to identify causative variants. A novel homozygous frameshift variant (c.1799_1805dupGTCTGGT) was identified in one family and two previously reported missense variants (c.2294G > A and c.2974G > A) in compound heterozygous form in the other family. We identified ABCC6 variants that are likely cause of the PXE disease in the tested families.
Conclusion Genetic analysis of these families could be useful for pre-symptomatic diagnosis and genetic counselling of the affected families.