Abstract
PurposeTo 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.MethodsIn 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 VSX1, TGFBI, and ZEB1 genes and full clinical assessment including Pentacam Scheimpflug tomography were carried out in these individuals.ResultsFive variants in VSX1 and TGFBI 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.ConclusionsVariants of VSX1 and TGFBI 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.
Highlights
Keratoconus (KC, OMIM 148300) is a bilateral noninflammatory ectasia disorder, sometimes asymmetric and characterized by progressive thinning, bulging, and a conical protrusion of the cornea (Krachmer et al, 1984; Rabinowitz, 1998)
We summarized 40 candidate genes related to KC (Supplementary Table 2), based on several genetics reviews of KC and PubMed database (Bykhovskaya et al, 2016; Loukovitis et al, 2018; Panahi et al, 2019)
According to the preliminary diagnosis, 91 patients were diagnosed as having KC, including 88 probands in all families and three first-degree relatives in two Greek families (G1, G2)
Summary
Keratoconus (KC, OMIM 148300) is a bilateral noninflammatory ectasia disorder, sometimes asymmetric and characterized by progressive thinning, bulging, and a conical protrusion of the cornea (Krachmer et al, 1984; Rabinowitz, 1998) It is a relatively common disease with a prevalence ranging from 0.3 to 2,300 per 100,000, affecting both genders and diverse populations around the world (Gokhale, 2013), with higher frequency among certain ethnicities such as in Asians and Middle Easterns (Kok et al, 2012; Gokhale, 2013). Most studies suggest an autosomal dominant mode of inheritance with different variable expressivity (Wang et al, 2000; Rabinowitz, 2003; Romero-Jimenez et al, 2010) These findings support the dominant role of a genetic factor in the pathogenesis of KC
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