Pseudoxanthoma elasticum (PXE) is a rare, autosomal-recessive disorder, characterized by ectopic mineralization and fragmentation of elastic fibers of connective tissues. Organs primarily affected are skin, eyes and cardiovascular system. PXE is caused by loss of function mutations in the ABCC6 gene, encoding an ATP-binding cassette protein which functions as an efflux transporter.

A molecular analysis of 306 French PXE probands, the largest cohort ever published, was performed including sanger sequencing of all 31 exons, multiplex PCR focusing the recurrent deletion including exons 23 to 29, and MLPA. In 239 patients the phenotype based on Phenodex score (PS) was well characterized. Genotype-phenotype correlation analysis was performed using 2 groups of patients: a first one with complete haploinsufficiency of the gene (group H: patients with 2 predicted loss-of-function variants), and a second one with predicted residual conservation of the transporter function (group M: patients with 2 missense mutations).

The molecular analysis led to the identification of 142 distinct mutations with 66 novel mutations and a detection rate of 88%. 3 groups of patients were distinguished according to the molecular status, ie corresponding to 0, 1 or 2 identified mutations. The mean PS in groups 2 and 3 were respectively S0E2G0V0C0, and S2E2/E3G0V0C0. Based on PS, statistical analysis revealed a tendency to a more severe phenotype in patients in group H than in group M, particularly in terms of vascular involvement. However, a more precise analysis of the patients phenotype revealed a prevalence of 11% of renal lithiasis, and of 10% of strokes or neurological sequelae of ischemia, that are not included in the PS. This particular point is discussed and a revised PS is proposed on the bases of the French cohort phenotypic characterization, as well as specific vascular care and prevention based on the patients molecular status.

The author hereby declares no conflict of interest