PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. ResultsĦ.4% of ABCC6-negative PXE patients ( n = 3) harboured biallelic pathogenic variants in CYP2U1. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Methodsįirst, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. We searched for new PXE gene(s) to solve the ABCC6-negative patients. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants.
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