Mutation Detection in Patients with Retinal Dystrophies Using Targeted Next Generation Sequencing

Abstract

Retinal dystrophies (RD) constitute a group of blinding diseases that are characterized by clinical variability and pronounced genetic heterogeneity. The different nonsyndromic and syndromic forms of RD can be attributed to mutations in more than 200 genes. Consequently, next generation sequencing (NGS) technologies are among the most promising approaches to identify mutations in RD. We screened a large cohort of patients comprising 89 independent cases and families with various subforms of RD applying different NGS platforms. While mutation screening in 50 cases was performed using a RD gene capture panel, 47 cases were analyzed using whole exome sequencing. One family was analyzed using whole genome sequencing. A detection rate of 61% was achieved including mutations in 34 known and two novel RD genes. A total of 69 distinct mutations were identified, including 39 novel mutations. Notably, genetic findings in several families were not consistent with the initial clinical diagnosis. Clinical reassessment resulted in refinement of the clinical diagnosis in some of these families and confirmed the broad clinical spectrum associated with mutations in RD genes.

The use of targeted genomic capture and massively parallel sequencing in diagnosis of Chinese Leukoencephalopathies

“…In recent years, targeted capture and MPS technologies have been widely used in clinical practice and have got satisfactory results15232425262728. To this end, we designed the gene panel contains 118 genes which are reported to be associated with leukoencephalopathies, not only contains genes associated with genetic leukoencephalopathy, but also mitochondrial disease, cerebral cortical degenerative disorders, etc.…”

Genome-Wide Detection of Copy Number Variations in Unsolved Inherited Retinal Disease

“…5,6 Among these identified IRD genes, the top leading ones include USH2A, EYS, ABCA4, PDE6B, RPGR, and RHO. [7][8][9][10][11][12][13] However, a definitive molecular diagnosis of IRD remains extremely complex and challenging because mutations are only detected in 40% to 60% of cases. 4,8,[14][15][16] Most of the previous studies of IRDs have focused on single-base substitution mutations or small insertions/deletions; however, it is reasonable to speculate that large duplications or deletions can also contribute to IRDs.…”

A Report on Molecular Diagnostic Testing for Inherited Retinal Dystrophies by Targeted Genetic Analyses

“…Over 250 genes have been implicated in causing IRD (RetNet) (Daiger et al, 1998). Genetic testing has the potential to accurately diagnose and predict disease occurrence in early and late-onset IRD Tajiguli et al, 2016;Weisschuh et al, 2016). Finding the genetic basis of IRDs is the first step of recruitment into gene mutation-based clinical trials (Wiggs and Pierce, 2013;Chiang and Trzupek, 2015;Lee and Garg, 2015;Nash et al, 2015).…”