Novel GLA Deletion in a Cypriot Female Presenting with Cornea Verticillata

• Published in: Case reports in genetics Vol. 2016; no. 2016; pp. 1 - 6
• Main Authors: Drousiotou, Anthi, Tanteles, George A., Sismani, Carolina, Krasia, Maria, Christodoulides, Theodoros, Savva, Isavella, Spanou-Aristidou, Elena, Alexandrou, Angelos, Mavrikiou, Gavriella, Georgiou, Theodoros, Anastasiadou, Violetta
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Case Report; DNA sequencing; Enzymes; Nucleotide sequencing
• ISSN: 2090-6544; 2090-6552
• DOI: 10.1155/2016/5208312

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.