Topographic characteristics of keratoconus among a sample of Jordanian patients

<b>AIM:</b>To identify topographic characteristics of keratoconus in a Jordanian sample.<b>METHODS</b>:This study characterized 210 corneas affected with keratoconus presenting to Jordan University Hospital. Patients were diagnosed based on clinical examinations and Pentacam imaging. Eyes of males (<i>n=</i>101) were of a similar proportion to females (<i>n=</i>109). All of the 111 patients were affected bilaterally. Ages ranged between 13 and 44y with a mean age of 25.2y.<b>RESULTS</b>:Results revealed significant differences between males and females at the level of the flat curvature power, basement membrane thickness and size of the anterior chamber. Eyes were arranged in three groups based on severity levels:mild, moderate and severe determined by the mean curvature power (Km). Results show that the flat (K1) and steep (K2) curvature powers, corneal asphericity coefficient (QV), thinnest point, pachy apex and basement membrane thickness are significantly different among the three groups, but not the corneal and anterior chamber volumes. Morphological analyses, based on sagittal maps, show no differences in keratometric values between eyes with different sagittal patterns except for the vertical location of the pachy apex relative to the pupil center and the thinnest point. Eyes with the island front elevation map are significantly more affected than eyes with the U shape and the ridge pattern.<b>CONCLUSION</b>:All keratometric values measured except for corneal and anterior chamber volumes vary significantly with disease severity. The vertical pachy apex location correlates well with severity levels while the horizontal location seems to have no effect. Our study also indicates that front elevation maps may be a better predictor of the severity of keratoconus than sagittal maps

Extending the spectrum of CLRN1‐ and ABCA4‐associated inherited retinal dystrophies caused by novel and recurrent variants using exome sequencing

Abstract Background Inherited retinal dystrophies (IRDs) are characterized by extreme genetic and clinical heterogeneity. There are many genes that are known to cause IRD which makes the identification of the underlying genetic causes quite challenging. And in view of the emergence of therapeutic options, it is essential to combine molecular and clinical data to correctly diagnose IRD patients. In this study, we aimed to identify the disease‐causing variants (DCVs) in four consanguineous Jordanian families with IRDs and describe genotype–phenotype correlations. Methods Exome sequencing (ES) was employed on the proband patients of each family, followed by segregation analysis of candidate variants in affected and unaffected family members by Sanger sequencing. Simulation analysis was done on one novel CLRN1 variant to characterize its effect on mRNA processing. Clinical evaluation included history, slit‐lamp biomicroscopy, and indirect ophthalmoscopy. Results We identified two novel variants in CLRN1 [(c.433+1G>A) and (c.323T>C, p.Leu108Pro)], and two recurrent variants in ABCA4 [(c.1648G>A, p.Gly550Arg) and (c.5460+1G>A)]. Two families with the same DCV were found to have different phenotypes and another family was shown to have sector RP. Moreover, simulation analysis for the CLRN1 splice donor variant (c.433+1G>A) showed that the variant might affect mRNA processing resulting in the formation of an abnormal receptor. Also, a family that was previously diagnosed with nonsyndromic RP was found to have Usher syndrome based on their genetic assessment and audiometry. Conclusion Our findings extend the spectrum of CLRN1‐ and ABCA4‐associated IRDs and describe new phenotypes for these genes. We also highlighted the importance of combining molecular and clinical data to correctly diagnose IRDs and the utility of simulation analysis to predict the effect of splice donor variants on protein formation and function