AUTHOR=Lofaro Francesco Demetrio , Mucciolo Dario Pasquale , Murro Vittoria , Pavese Laura , Quaglino Daniela , Boraldi Federica 

TITLE=From Clinical Diagnosis to the Discovery of Multigene Rare Sequence Variants in Pseudoxanthoma elasticum: A Case Report

JOURNAL=Frontiers in Medicine

VOLUME=8

YEAR=2021

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2021.726856

DOI=10.3389/fmed.2021.726856

ISSN=2296-858X

ABSTRACT=<p><italic>Pseudoxanthoma elasticum</italic> (PXE) is a rare autosomal recessive disease clinically characterised by early cutaneous alterations, and by late clinically relevant ocular, and cardiovascular manifestations. <italic>ABCC6</italic> genetic tests are used to confirm clinical PXE diagnosis, but this strategy may be rather challenging when only one <italic>ABCC6</italic> pathogenic variant is found. A next-generation sequencing approach focusing on 362 genes related to the calcification process and/or to inherited retinal diseases was performed on a patient with clinical PXE diagnosis (skin papules and laxity, angioid streaks, and atrophy) who was carrier of only one <italic>ABCC6</italic> rare sequence variant. Beside <italic>ABCC6</italic>, several rare sequence variants were detected which can contribute either to the occurrence of calcification (<italic>GGCX</italic> and <italic>SERPINF1</italic> genes) and/or to ophthalmological manifestations (<italic>ABCA4, AGBL5, CLUAP1</italic>, and <italic>KCNV2</italic> genes). This wide-spectrum analysis approach facilitates the identification of rare variants possibly involved in PXE, thus avoiding invasive skin biopsy as well as expensive and time-consuming diagnostic odyssey and allows to broaden and to deepen the knowledge on this complex rare disease and to improve patients' counselling, also with a future perspective of personalised medicine.</p>