Confirmation of association of TGFBI p.Ser591Phe mutation with variant lattice corneal dystrophy. (4th July 2022)

• Record Type: Journal Article
• Authors: Choo, Charlene H.; Chung, Doug D.; Ledwitch, Kaitlyn V.; Kassels, Alexa; Meiler, Jens; Aldave, Anthony J.
• Is Part Of: Ophthalmic genetics. Volume 43:Number 4(2022)
• Page Start: 530
• Page End: 533
• Publication Date: 2022-07-04
• Subjects: Lattice corneal dystrophy (LCD) -- unilateral LCD -- asymmetric LCD -- transforming growth factor-β-induced (TGFBI); Eye -- Diseases -- Genetic aspects -- Periodicals; Eye Diseases -- genetics -- Periodicals; Eye Diseases -- in infancy & childhood -- Periodicals; 617.7
• DOI: 10.1080/13816810.2022.2050766
• Languages: English
• ISSNs: 1381-6810

Abstract

ABSTRACT: Purpose: To provide the initial confirmation of the c.1772C>T (p.Ser591Phe) mutation in the transforming growth factor- β -induced ( TGFBI) gene as being associated with variant lattice corneal dystrophy (LCD). Methods: Ophthalmologic examination of the proband was performed with slit lamp biomicroscopy. Saliva was collected as a source of DNA for screening all 17 exons of TGFBI, after which three family members were selectively screened for variants in exon 13. Rosetta-based structure prediction was used to calculate changes in TGFBI protein (TGFBIp) stability secondary to the c.1772C>T (p.Ser591Phe) missense mutation. Results: Slit lamp examination of the 38-year-old proband revealed a clear cornea right eye and unilateral, discrete, and branching lattice lines in the anterior and mid-stroma of the central cornea left eye. Screening of TGFBI in the proband revealed a heterozygous missense mutation in exon 13 (c.1772C>T (p.Ser591Phe)) that was also identified in her affected mother but not in her brother or maternal grandmother. Calculated energy change in Rosetta (ΔΔG) for the TGFBIp variant p.Ser591Phe was 23.5, indicating a thermodynamic destabilization resulting from energetic frustration. Conclusions: The p.Ser591Phe mutation in TGFBI is associated with an unilateral variant of LCD. Rosetta-predicted stability changes indicate that the p.Ser591Phe variant is destabilizing, which is consistent with other observations for LCD-causing mutations.