Inherited retinal dystrophies (IRDs) are a group of clinically and genetically heterogeneous diseases involving more than 280 genes and no less than 20 different clinical phenotypes. In this study, our aims were to identify the disease-causing gene variants of 319 Chinese patients with IRD, and compare the pros and cons of targeted panel sequencing and whole exome sequencing (WES). Patients were assigned for analysis with a hereditary eye disease enrichment panel (HEDEP) or WES examination based on time of recruitment. This HEDEP was able to capture 441 hereditary eye disease genes, which included 291 genes related to IRD. As RPGR ORF15 was difficult to capture, all samples were subjected to Sanger sequencing for this region. Among the 163 disease-causing variants identified in this study, 73 had been previously reported, and the other 90 were novel. Genes most commonly implicated in different inheritances of IRDs in this cohort were presented. HEDEP and WES achieved diagnostic yield with 41.2% and 33.0%, respectively. In addition, nine patients were found to carry pathogenic mutations in the RPGR ORF15 region with Sanger sequencing. Our study demonstrates that HEDEP can be used as a first-tier test for patients with IRDs.

AimsTo elucidate genetic background of early-onset high myopia (eoHM) and characteristics of ARR3-associated MYP26.MethodsVariants in 14 genes reported to contribute to eoHM, including ARR3, were selected from exome sequencing data set and classified into different categories following American College of Medical Genetics and Genomics guidelines based on in silico prediction, associated phenotypes, confirmation and cosegregation analysis. The available clinical data of individuals were summarised.ResultsPathogenic and likely pathogenic variants in three of 14 genes were identified in 52 of 928 families with eoHM, including 29 in ARR3, 22 in OPN1LW and 1 in LRPAP1. For ARR3, 24 pathogenic variants (16 truncation and 8 missense) were identified in 66 women and 12 men, in whom 64 women and 4 men had eoHM by X-linked female-limited inheritance. Refraction ranged from −5.00 to −28.75 diopter (−12.58±4.83). Mild-to-moderately reduced cone responses were recorded in 76.9% (10/13) of patients with electroretinogram recordings. Most patients (75.9%, 41/54) had mild myopic fundus changes (C0 to C1). Genotype–phenotype analysis suggested that the myopic retinopathy degree was correlated with age and the variant’s nature. Peripheral retinal degeneration was observed in 38.5% (5/13) patients using wide-field examinations.ConclusionThis study reveals ARR3 as the most frequently implicated gene for Mendelian eoHM. Truncations and highly scored missense variants in ARR3 are pathogenic. Myopia due to ARR3 mutations is transmitted in X-linked female-limited inheritance, manifests with mild cone impairment and slowly progresses to pathologic myopia. Identification of the most common cause for Mendelian eoHM provides a valuable starting point into the molecular mechanism of myopia.

No abstract

A Monte Carlo method for holistically simulating optical coherence tomography (OCT) has been developed. The geometrical optics implementation of OCT probe optical system was combined with Monte Carlo simulation for photon propagation in homogeneous turbid media to simulate OCT signal. The hyperboloid model to describe Gaussian beam's photon propagation made the simulation more accurate, and the importance sampling method has been used to accelerate the simulation process. We made the experimental measurements and simulations for Intralipid TM samples with different concentrations. Both the measured and simulated results show that the high scattering coefficient and weakly forward scattering are the primary causes for the attenuation of OCT signal as the focusing depth increases, and the OCT imaging resolution also decreases with the increase of focusing depth. The focusing plane curvature caused by scanning the fibretip laterally near the front focal plane of the OCT probe optical system deforms the OCT image and results in the decrease of image resolution also. It is also found that the effect of the numerical aperture (NA) of the fibretip on OCT signal depends on the value of NA. For a given OCT probe optical system, there is a best numerical range for NA.