A Novel Heterozygous TGFBI c.1613C>A Pathogenic Variant is Associated With Lattice Corneal Dystrophy in a Chinese Family.

Purpose: To investigate the gene mutations and relationship of clinical manifestation in a Chinese family with familial lattice corneal dystrophy (LCD).

Design: Single-family case-control study.

Methods: A family with familial LCD was recruited for this study. A total of 10 affected and 13 healthy family members participated in this research. Clinical features were examined by slit-lamp examination and anterior segment optical coherence tomography (AS-OCT). Peripheral blood samples were collected from each participant, and genomic DNA was extracted. Whole-exome sequencing (WES) analysis was performed, and the pathogenic variants of LCD were identified using bioinformatics tools and confirmed by Sanger sequencing.

Results: Slit-lamp examination revealed diffuse grayish-white punctate, linear, and "lattice-like" opacities in the corneal epithelium and superficial corneal stroma. AS-OCT revealed an irregularly shaped cornea. The corneal epithelium and anterior corneal stroma showed high-reflective deposits and bulges. The clinical appearance of the patients fit the pattern and features of autosomal dominant inheritance of LCD type I (LCD I). A novel pathogenic variant of exon 12 in TGFBI was found by WES analysis, in which cytosine at position 1613 was substituted by adenine (c.1613C>A), and the amino acid was changed from threonine to lysine (p.T538K). Mutated genes and proteins were predicted to be deleterious.

Conclusion: A novel heterozygous pathogenic variant (c.1613C>A) of TGFBI was identified in the Chinese family with LCD I.