Abstract
Purpose :
Mutations in the TGFBI (BIGH3) gene are known to cause autosomal dominant corneal dystrophies. The clinically distinct phenotypes of these dystrophies are related to the location of the mutation in the gene. We describe a new corneal dystrophy phenotype, with no resemblance to any of the already known phenotypes, in a patient also suffering from adult-onset-vitelliform macular dystrophy (AOVMD).
Methods :
We performed a complete ophthalmic work-up including biomicroscopy, corneal photography, anterior segment and macula SD-OCT, and confocal microscopy. Additionally, laboratory blood tests and Whole Exome Sequencing (WES) were carried out.
Results :
A 63-years old woman presented with visual loss in her right eye caused by AOVMD. Her family history was negative for ophthalmic diseases. Biomicroscopy revealed mid-peripheral concentric, ring-shaped, deep stromal immunoglobulin-deposition-like opacities in both corneas.
With laboratory testing, M-protein, immunoglobulins, and cryoglobulins were all tested negative. WES revealed a heterozygous missense mutation in TGFBI (c.1998G>C, p.Arg666Ser). .
Conclusions :
We present a not previously described phenotype of stromal corneal dystrophy and AOVMD with a mutation in TGFBI. The found gene mutation has previously only been reported in one family with Epithelial Basement Membrane Corneal Dystrophy.1 Neither the mutation, nor the phenotype has been previously described in TGFBI-associated stromal corneal dystrophies.2 An association of the mutation with AOVMD may be plausible since retinal and RPE abnormalities have been observed in knock-out and transgenic mice in the presence of TGFBI mutations.3,4
References:
1. A subset of patients with Epithelial Basement Membrane Corneal Dystrophy have mutations in TGFBI/BIGH3. Boutboul S, Black GCM, Moore JE, et al. Human Mutation 2006:27;553-7.
2. IC3D Classification of Corneal Dystrohphies. Edition 2. Weiss JS, Moeller HU, Aldave AJ, et al. Cornea 2015:34; 117-159
3. Overexpression of TGFBI/BIGH3 induces retinal degeneration in transgenic mice. Bustamante M, Tasinato A, Maurer F, et al. Mol Vis 2008;14:1129-37
4. TGFBI/BIGH3 silencing activates ERK in mouse retina. Allaman-Pillet N, Obreson A, Bustamante M, et al. Exp Eye Res 2015;140:159-70
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.