Novel GLA Deletion in a Cypriot Female Presenting with Cornea Verticillata

الملخص EN

Fabry disease is an X-linked lysosomal storage disorder resulting from a deficiency of the hydrolytic enzyme α-galactosidase A (α-Gal-A).

It is characterized by progressive lysosomal accumulation of globotriaosylceramide (Gb3) and multisystem pathology, affecting the skin, nervous and cerebrovascular systems, kidneys, and heart.

Heterozygous females typically exhibit milder symptoms and a later age of onset than males.

Rarely, they may be relatively asymptomatic throughout a normal life span or may have symptoms as severe as those observed in males with the classic phenotype.

We report on a 17-year-old female in whom cornea verticillata was found during a routine ophthalmological examination but with no other clinical symptoms.

Leucocyte α-galactosidase activity was within the overlap range between Fabry heterozygotes and normal controls.

Sanger sequencing of the GLA gene failed to reveal any pathogenic variants.

Multiplex Ligation-dependent Probe Amplification (MLPA) analysis revealed a deletion of exon 7.

Using a long-range PCR walking approach, we managed to identify the deletion breakpoints.

The deletion spans 1182 bp, with its 5′ end located within exon 6 of the GLA gene and its 3′ end located 612 bp downstream of exon 7.

This finding represents a novel deletion identified in the first reported Cypriot female carrier of Fabry disease.