Abstract
Purpose :
To identify underlying mutations in five Pseudoxanthoma Elasticum (PXE) patients of different ethnicities with variable disease expression.
Methods :
Five affected individuals (two sib-pairs and a single patient) were recruited. Medical history, clinical findings and OCT were recorded. Mutation analysis of ABCC6 gene was carried out by both Sanger sequencing and whole-exome sequencing (WES).
Results :
Various retinal findings ranging from peau d'orange, angioid streaks and CNV to severe retinal atrophy were documented. Skin papules were found in both sib-pairs, but were absent in the single patient (P3), who demonstrated severe retinal changes. He was found to be a compound heterozygote to two novel ABCC6 mutations – a missense mutation (p.G1475E), and a frame-shift mutation causing single nucleotide deletion (c.1413delG). Siblings P1 and P2 were found to carry a homozygous splice site mutation by WES (c.3883-6G>A). Siblings P4 and P5 were found to carry a heterozygous compound missense and a nonsense variant (p.R1064W, p.R1141*).
Conclusions :
Our study stresses the significance of thorough history taking and clinical examination when evaluating patients suspected for PXE. It expands the repertoire of PXE mutations, presenting two novel mutations contributing to compound heterozygosity in a patient with an irregular phenotype. Finally, it highlights the role of genetic tools in present and future medical practice, empowering the physician to achieve diagnosis through molecular methods.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.