AUTHOR=Chen Shihao , Li Xing-Yong , Jin Jia-Jia , Shen Ren-Juan , Mao Jian-Yang , Cheng Fei-Fei , Chen Zhen-Ji , Linardaki Emmanouela , Voulgaraki Stavroula , Aslanides Ioannis M. , Jin Zi-Bing 

TITLE=Genetic Screening Revealed Latent Keratoconus in Asymptomatic Individuals

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.650344

DOI=10.3389/fcell.2021.650344

ISSN=2296-634X

ABSTRACT=<sec><title>Purpose</title><p>To adopt molecular screening in asymptomatic individuals at high risk of developing keratoconus as a combinative approach to prevent subclinical patients from post-refractive surgery progressive corneal ectasia.</p></sec><sec><title>Methods</title><p>In this study, 79 Chinese and nine Greek families with keratoconus were recruited, including 91 patients with clinically diagnosed keratoconus as well as their asymptomatic but assumptive high-risk first-degree relatives based on underlying genetic factor. Mutational screening of <italic>VSX1</italic>, <italic>TGFBI</italic>, and <italic>ZEB1</italic> genes and full clinical assessment including Pentacam Scheimpflug tomography were carried out in these individuals.</p></sec><sec><title>Results</title><p>Five variants in <italic>VSX1</italic> and <italic>TGFBI</italic> genes were identified in three Chinese families and one Greek family, and four of them were novel ones. Surprisingly, ultra-early corneal changes in Belin/Ambrosio Enhanced Ectasia Display of Pentacam corneal topography together with co-segregated variants were revealed in the relatives who had no self-reported symptoms.</p></sec><sec><title>Conclusions</title><p>Variants of <italic>VSX1</italic> and <italic>TGFBI</italic> genes identified in both the clinically diagnosed and subclinical patients may cause the keratoconus through an autosomal dominant inheritance pattern, with different variable expressivity. Combining genetic with Belin/AmbrosioEnhanced Ectasia Display can be used to identify patients with latent keratoconus. This study indicates that genetic testing may play an important supplementary role in re-classifying the disease manifestation and evaluating the preoperative examination of refractive surgery.</p></sec>