Fleck corneal dystrophy in a black South African family : a case series

Camacho, Monique De Gouveia
Journal Title
Journal ISSN
Volume Title
Background Corneal dystrophies are genetically determined non-inflammatory corneal diseases. Fleck corneal dystrophy (FCD) is a rare autosomal dominant condition caused by a mutation in the phosphoinositide kinase FYVE finger (PIKFYVE) gene. There are few descriptions of FCD in the literature and no known studies on the genetics of this condition in sub-Saharan Africa. Purpose To describe the clinical features of FCD within a black South African family and to apply targeted sequencing for variant identification in the PIKFYVE gene. Patients and Methods Clinical Examination Ten family members from three generations were examined using slit-lamp microscopy, corneal tomography and ocular coherence tomography. Genetic Material Collection & Data Analysis Saliva and blood samples were collected and targeted sequencing of exon 19 of PIKFYVE was completed using Sanger sequencing. Variants were identified and mapped. Results We found flecks in six individuals, five of whom had posterior embryotoxon. Six variants on exon 19 of PIKFYVE were identified across all family members. These include four previously identified missense variants, rs893253 (p.Thr998Ser), rs893254 (p.Gln995Leu), rs1529979 (p.Gln1183Lys) and rs999890 (p.Ser1033Ala); and two non-synonymous variants, rs1529978 (p.Asn1188=) and rs999891 (p.Arg1038=). Rs999891 has not been reported in association with FCD before. All variants were categorised as benign and identified in both cases and controls. Conclusion No pathogenic mutations were identified in this family that could account for the FCD. We replicated associations reported in the literature but did not find evidence to suggest that they were responsible for the phenotype. Further research is required along with expanded sequencing of the entire gene to better characterize the association of FCD with the PIKFYVE gene.
A research report submitted in partial fulfilment of the requirements for the degree of Master of Medicine in Ophthalmology to the Faculty of Health Sciences, School of Clinical Medicine, University of the Witwatersrand, Johannesburg, 2022