Novel GLA Deletion in a Cypriot Female Presenting with Cornea Verticillata.
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.
Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Theodoros
T
Georgiou
Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Gavriella
G
Mavrikiou
Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Angelos
A
Alexandrou
Clinical Genetics Department, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Elena
E
Spanou-Aristidou
Molecular Medicine Research Center, University of Cyprus, 1678 Nicosia, Cyprus.
Isavella
I
Savva
Cardio Health Center, 2042 Nicosia, Cyprus.
Theodoros
T
Christodoulides
Ophthalmology Centre, 2223 Nicosia, Cyprus.
Maria
M
Krasia
Clinical Genetics Department, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Violetta
V
Christophidou-Anastasiadou
Department of Cytogenetics and Genomics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Carolina
C
Sismani
Department of Biochemical Genetics, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
Anthi
A
Drousiotou
Clinical Genetics Department, The Cyprus Institute of Neurology and Genetics, 2370 Nicosia, Cyprus.
George A
GA
Tanteles