Premium
c.‐61G>A in OVOL2 is a pathogenic variant in posterior polymorphous corneal dystrophy 1—a case report
Author(s) -
JaneschitzKriegl Lucas,
Rivolta Carlo,
György Bence,
Quinodoz Mathieu,
Meyer Peter,
Wild Andreas,
Escher Pascal,
Scholl Hendrik,
Goldblum David
Publication year - 2021
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2020.0178
Subject(s) - medicine , ophthalmology , pathology
Purpose To investigate the clinical and genetic features of a man and his daughter with Posterior polymorphous corneal dystrophy 1 (PPCD1), referred to our clinic for Descemet's Membrane Endothelial Keratoplasty (DMEK). No other known relatives were affected, including the index patient's spouse and their son. Methods Clinical examination was performed by best‐corrected visual acuity (BCVA) testing, slit‐lamp examination (SLE), anterior‐segment optical coherency tomography (OCT) and specular microscopy. Histologic testing and electron microscopy were done. Genetic testing was carried out by means of Whole‐Exome Sequencing (WES), and variant analysis was achieved by an internal in silico pipeline. Results Slowly progressive blurred vision was reported from childhood by the daughter. The father's symptoms started approximately ten years prior to consultation. BCVA was 0.2 in both eyes in the father and 0.2/0.4 in the right/left eye in the daughter. SLE in both patients revealed bilateral corneal clouding with focal grey endothelial spots. Corneal edema with Descemet's folds was present. DMEK was performed uneventfully. Histology and electron microscopy showed layered Descemet's membrane and pleomorphic endothelial cells with vacuoles but no microvilli. Genetic analysis revealed the c. ‐61G>A variant in the 5′UTR region of the OVOL2 gene heterozygously, in both patients. This change was not present in the unaffected members of the family. Conclusions PPCD1 has been linked to mutations in the promoter and the 5′UTR region of OVOL2 . The NM_021220.4:c.‐61G>A DNA change was previously reported as a variant of unknown pathogenicity, despite having been identified in another patient with PPCD1. Based on perfect familial co‐segregation, complete absence of this change in all public databases of normal controls, and its identification in two additional individuals with PPCD1, we conclude that c.‐61G>A is a truly pathogenic mutation for this condition.