Identification of A Novel TGFBI Gene Mutation (p.Serine524Cystine) Associated with Late Onset Recurrent Epithelial Erosions and Bowman Layer Opacities

• Published in: Ophthalmic genetics Vol. 41; no. 6; pp. 639 - 644
• Main Authors: Chen, Angela C, Niruthisard, Duangratn, Chung, Doug D, Chuephanich, Pichaya, Aldave, Anthony J
• Format: Journal Article
• Language: English
• Published: England 01-12-2020
• Subjects: Age of Onset; Autoantigens - genetics; Bowman Membrane - metabolism; Bowman Membrane - pathology; Collagen Type XVII; Corneal Dystrophies, Hereditary - genetics; Corneal Dystrophies, Hereditary - pathology; Epithelium, Corneal - metabolism; Epithelium, Corneal - pathology; Extracellular Matrix Proteins - genetics; Female; Humans; Male; Middle Aged; Mutation; Non-Fibrillar Collagens - genetics; Pedigree; Phenotype; Recurrence; Slit Lamp Microscopy; Transforming Growth Factor beta - genetics; TGFBI; TGFBI corneal dystrophy; recurrent epithelial erosions; Bowman layer dystrophy
• ISSN: 1381-6810; 1744-5094
• DOI: 10.1080/13816810.2020.1814345

Most transforming growth factor beta-induced (
) corneal dystrophies are associated with a characteristic phenotype, clinical course, and a conserved mutation in the
gene. However, we report a novel
missense mutation associated with a late-onset, variant Bowman layer dystrophy.
Participants underwent slit-lamp examination and multimodal imaging. Polymerase chain reaction amplification and Sanger sequencing were performed on saliva-derived genomic DNA to screen
exons 4 and 12 as well as
exon 46. PolyPhen-2 and SIFT were used to predict the functional impact of any identified variants.
A 56-year-old Thai woman reported a four-year history of decreased vision and intermittent eye irritation, suggestive of recurrent epithelial erosions, in both eyes. Slit-lamp exam revealed bilateral, irregular, limbal-sparing Bowman layer opacities, which were also noted on anterior segment optical coherence tomography. Phototherapeutic keratectomy was performed in the right eye, improving the best-corrected visual acuity from 20/50 to 20/30. Sequencing of the
gene revealed a novel heterozygous, missense mutation in exon 12 (c.1571 C > G; p.Ser524Cys), which was present in an affected son and absent in an unaffected son, and was predicted to be damaging by PolyPhen-2 and SIFT. The patient was diagnosed with a variant Bowman layer dystrophy given the late onset of an atypical phenotype and the identification of a novel
mutation.
A novel
missense mutation is associated with a late-onset Bowman layer dystrophy. Given the atypical clinical appearance and course, molecular genetic analysis was utilized to establish a definitive diagnosis.