A novel variant in TGFBI causes keratoconus in a two-generation Chinese family

• Published in: Ophthalmic genetics Vol. 43; no. 2; pp. 159 - 163
• Main Authors: Lin, Qinghong, Zheng, Lin, Shen, Zhengwei
• Format: Journal Article
• Language: English
• Published: England 01.04.2022
• Subjects: Asians - genetics; China - epidemiology; Corneal Dystrophies, Hereditary - genetics; DNA Mutational Analysis; Extracellular Matrix Proteins - genetics; Humans; Keratoconus - diagnosis; Keratoconus - genetics; Mutation; Pedigree; Polymorphism, Single Nucleotide; Transforming Growth Factor beta - genetics; Transforming Growth Factor beta1; China; Keratoconus; TGFBI; genetic variant
• ISSN: 1381-6810; 1744-5094; 1744-5094
• DOI: 10.1080/13816810.2021.2015788

This study aims to investigate the genetic abnormalities in a two-generation Chinese family affected by keratoconus (KC). A two-generation Chinese family affected by KC was studied. A total of 118 unrelated healthy individuals without KC were recruited as controls. The family history, clinical data, and peripheral blood leukocytes were collected from all subjects. Whole exome sequencing was performed using the genomic DNA of the proband (II.2) and the other two affected family members (I.1 and II.3). Afterwards, polymerase chain reaction was performed for the other enrolled subjects to verify the variants identified in family members with KC. The PolyPhen2, SIFT, PROVEIN and Mutation Taster software programs were applied to analyze the functional consequences of the variants. A single nucleotide polymorphism (VARIANT) (c.1406 G > A [rs759370852]) in the transforming growth factor beta-induced ( ) gene was identified in all affected family members, which resulted in a p.R469H amino acid change. This variant was not detected in the controls. The variant c.1406 G > A in was predicted as probably damaging with software programs. A novel variant c.1406 G > A in has been identified, and probably contributes to the pathogenesis of KC.