c.-61G>A in OVOL2 is a Pathogenic 5' Untranslated Region Variant Causing Posterior Polymorphous Corneal Dystrophy 1.

Janeschitz-Kriegl, Lucas; Kamdar, Dhryata; Quinodoz, Mathieu; Kaminska, Karolina; Folcher, Marc; György, Bence; Meyer, Peter; Wild, Andreas; Escher, Pascal; Scholl, Hendrik P N; Rivolta, Carlo; Goldblum, David (2022). c.-61G>A in OVOL2 is a Pathogenic 5' Untranslated Region Variant Causing Posterior Polymorphous Corneal Dystrophy 1. Cornea, 41(1), pp. 89-94. Wolters Kluwer Health 10.1097/ICO.0000000000002843

[img] Text
c__61G_A_in_OVOL2_is_a_Pathogenic_5__Untranslated.13.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (345kB)

PURPOSE

The purpose of this study was to investigate the clinical and genetic features of a man and his daughter with posterior polymorphous corneal dystrophy (PPCD), referred to our clinic for Descemet membrane endothelial keratoplasty. No other known relatives were affected.

METHODS

Ophthalmic examination and histology, including electron microscopy, were performed. Genetic testing was conducted by means of whole exome sequencing, and variant analysis was achieved by using an internal in silico pipeline. Molecular tests included a dual-luciferase assay.

RESULTS

Slowly progressive blurred vision was reported from childhood by the daughter. The father's symptoms started at age 55. Best-corrected visual acuity was reduced in both patients (0.2-0.4). Slit-lamp examination in both patients revealed bilateral corneal clouding with gray endothelial lesions; other family members had no ophthalmological signs. Descemet membrane endothelial keratoplasty was performed uneventfully in both patients. Histology showed thickened Descemet membrane and abnormal endothelium resembling epithelial-like cells. Both patients carried the OVOL2 5' untranslated region NM_021220.4.c.-61G>A variant in the heterozygous state. This change was associated with increased promoter activity and was not present in the unaffected members of the family.

CONCLUSIONS

The 5' untranslated region mutation c.-61G>A in OVOL2 has been previously found in 1 individual with PPCD1 and reported as a variant of unknown significance because of insufficient evidence supporting its pathogenicity. Identification of the second family with 2 individuals affected by PPCD1 carrying this change, together with functional data, provides further proofs that it is disease-causing.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Ophthalmology

UniBE Contributor:

Escher, Pascal

Subjects:

600 Technology > 610 Medicine & health
500 Science > 570 Life sciences; biology

ISSN:

1536-4798

Publisher:

Wolters Kluwer Health

Language:

English

Submitter:

Pascal Escher

Date Deposited:

19 Jan 2022 15:08

Last Modified:

05 Dec 2022 16:03

Publisher DOI:

10.1097/ICO.0000000000002843

PubMed ID:

34469340

BORIS DOI:

10.48350/164394

URI:

https://boris.unibe.ch/id/eprint/164394

Actions (login required)

Edit item Edit item
Provide Feedback