A novel ABCC6 variant causative of pseudoxanthoma elasticum

Gianluca Contrò,Rossana Tallerico,Stefano Dastoli,Emma Colao,Steven Paul Nisticò,Vincenzo Dattilo,Rodolfo Iuliano,Uros Hladnik,Fernanda Fabiani,Maria Vittoria Enzo,Nicola Perrotti

doi:10.1038/s41439-019-0062-x

Abstract

Pseudoxanthoma elasticum is an autosomal recessive heritable disorder caused by mutations in ABCC6. We describe two siblings showing typical skin lesions and a clinical diagnosis of pseudoxanthoma elasticum. Genetic analysis of ABCC6 revealed a novel homozygous c.4041G > A variant located in the last position of exon 28 that compromises the splicing donor site, resulting in a shorter messenger RNA. The deletion impairs the nucleotide-binding fold region, which is crucial for ABCC6 function.

Highlights

Pseudoxanthoma elasticum is an autosomal recessive heritable disorder caused by mutations in ABCC6
We detected a novel ABCC6 variant associated with PXE in two siblings, and clarified the functional effect of this variant
The first patient was an 18-year-old woman referred to our unit for the presence of the PXE typical skin alteration, at the age of 17, located on the lateral side of the neck, the axilla, and the upper side of the chest

Summary

Introduction

Pseudoxanthoma elasticum is an autosomal recessive heritable disorder caused by mutations in ABCC6. The causative gene of PXE was identified as adenosinebinding protein cassette 6 (ABCC6)[4], located on chromosome 16p13.1, encoding a transporter that carries various molecules across extra- and intracellular membranes. A wide range of ABCC6 mutations was previously reported as causative of different medical conditions characterized by altered mineralization in different tissues[5].

Results

Conclusion