Clinical and analytical validation of an 82-gene comprehensive genome-profiling panel for identifying and interpreting variants responsible for inherited retinal dystrophies.

Inherited retinal dystrophies comprise a clinically complex and heterogenous group of diseases characterized by visual impairment due to pathogenic variants of over 300 different genes. Accurately identifying the causative gene and associated variant is crucial for the definitive diagnosis and subsequent selection of precise treatments. Consequently, well-validated genetic tests are required in the clinical practice. Here, we report the analytical and clinical validation of a next-generation sequencing targeted gene panel, the PrismGuide IRD Panel System. This system enables comprehensive genome profiling of 82 genes related to inherited retinal dystrophies. The PrismGuide IRD Panel System demonstrated 100% (n = 43) concordance with Sanger sequencing in detecting single-nucleotide variants, small insertions, and small deletions in the target genes and also in assessing their zygosity. It also identified copy-number loss in four out of five cases. When assessing precision, we evaluated the reproducibility of variant detection with 2,160 variants in 144 replicates and found 100% agreement in terms of single-nucleotide variants (n = 1,584) and small insertions and deletions (n = 576). Furthermore, the PrismGuide IRD Panel System generated sufficient read depth for variant calls across the purine-rich and highly repetitive open-reading frame 15 region of RPGR and detected all five variants tested. These results show that the PrismGuide IRD Panel System can accurately and consistently detect single-nucleotide variants and small insertions and deletions. Thus, the PrismGuide IRD Panel System could serve as useful tool that is applicable in clinical practice for identifying the causative genes based on the detection and interpretation of variants in patients with inherited retinal dystrophies and can contribute to a precise molecular diagnosis and targeted treatments.

Formation of undulated lamellar structure from ABC block terpolymer blends with different chain lengths.

The effect of molecular weight distribution of ABC linear terpolymers on the formation of periodic structures was investigated. Three poly(isoprene-b-styrene-b-2-vinylpridine) triblockterpolymers with molecular weights of 26k, 96k, and 150k were blended variously. Three-phase, four-layer lamellar structures were observed when polydispersity index (PDI) was low, but it has been found that simple lamellar structure with flat surface transforms into an undulated lamellar one, where two interfaces, i.e., I/S and S/P, are both undulated, and they are synchronizing each other if PDI exceeds the critical value. This new structure could be formed due to the periodic and "weak" localization of three chains along the domain interfaces, which produces periodic surfaces with nonconstant mean curvatures. With further increase of PDI, the blend macroscopically phase-separated into different microphase-separated structures.

Miliary tuberculosis with indeterminate interferon gamma release assay results.

Recently, interferon gamma release assays (IGRAs) have become an important clinical tool for detecting latent tuberculosis. However, IGRA results may impede making a diagnosis. We herein present an interesting case of miliary tuberculosis with a nonspecific IGRA reaction due to hemophagocytosis.