ABCC6 gene mutational spectrum and ocular features in Mexican patients with pseudoxanthoma elasticum-related angioid...

Angioid streaks (AS) are uncommon retinal lesions associated with significant risk of vision loss due to choroidal neovascularization. About half of AS cases have a concurrent disease, most commonly pseudoxanthoma elasticum (PXE), a recessively inherited disorder that affects the skin, the eye, and vascular system and caused by biallelic mutations in the ABCC6 gene. In this work, we describe the ocular phenotype and the ABCC6 mutational profile in a cohort of 17 AS Mexican patients.

17 unrelated AS probands, with or without concurrent dermatologic features were studied. ABCC6 mutational analysis was performed employing next-generation sequencing (NGS) gene panel or exome sequencing.

Biallelic pathogenic variants in ABCC6 were demonstrated in 10 out of 17 (~60%) AS patients confirming a PXE diagnosis. In 4 individuals, only heterozygous ABCC6 variants were recognized while in 3 cases no mutations in AS-related genes were identified. A total of 7 previously unpublished ABCC6 disease-causing variants were identified in our cohort, including 5 missense, 1 frameshift, and 1 intragenic deletion.

In most subjects from our cohort, AS were due to genetically confirmed PXE, as previously observed in other ethnic groups. We expanded the ABCC6-related mutational spectrum by recognizing 7 previously unpublished pathogenic variants.