NGS-based Molecular diagnosis of 105 eyeGENE® probands with Retinitis Pigmentosa

Ge, Zhongqi; Bowles, Kristen E.; Goetz, Kerry; Scholl, Hendrik P. N.; Wang, Feng; Wang, Xinjing; Xu, Shaohua; Wang, Keqing; Wang, Hui; Chen, Rui

doi:10.1038/srep18287

Cited by 67 publications

(55 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the finding of USH2A and ABCA4 as the most mutated genes for RP/USH and STGD patients is consistent with previous reports [27–29]. In our RP cohort, USH2A is followed by CNGB1 and RPGR .…”

Section: Discussionsupporting

confidence: 93%

“…In our RP cohort, USH2A is followed by CNGB1 and RPGR . These two genes, already reported among the most frequently mutated genes in IRD patients [29], were not highly frequently altered in the Saudi population [6] or in a large cohort of Western European and South Asian individuals [27]. Also, we did not find any alteration in EYS , one of the top three genes contributing to IRD in other populations [28, 29].…”

Section: Discussionsupporting

confidence: 46%

See 1 more Smart Citation

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Bernardis

Chiesi

Tenedini

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

To assess the clinical utility of targeted Next-Generation Sequencing (NGS) for the diagnosis of Inherited Retinal Dystrophies (IRDs), a total of 109 subjects were enrolled in the study, including 88 IRD affected probands and 21 healthy relatives. Clinical diagnoses included Retinitis Pigmentosa (RP), Leber Congenital Amaurosis (LCA), Stargardt Disease (STGD), Best Macular Dystrophy (BMD), Usher Syndrome (USH), and other IRDs with undefined clinical diagnosis. Participants underwent a complete ophthalmologic examination followed by genetic counseling. A custom AmpliSeq™ panel of 72 IRD-related genes was designed for the analysis and tested using Ion semiconductor Next-Generation Sequencing (NGS). Potential disease-causing mutations were identified in 59.1% of probands, comprising mutations in 16 genes. The highest diagnostic yields were achieved for BMD, LCA, USH, and STGD patients, whereas RP confirmed its high genetic heterogeneity. Causative mutations were identified in 17.6% of probands with undefined diagnosis. Revision of the initial diagnosis was performed for 9.6% of genetically diagnosed patients. This study demonstrates that NGS represents a comprehensive cost-effective approach for IRDs molecular diagnosis. The identification of the genetic alterations underlying the phenotype enabled the clinicians to achieve a more accurate diagnosis. The results emphasize the importance of molecular diagnosis coupled with clinic information to unravel the extensive phenotypic heterogeneity of these diseases.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 46%

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Bernardis

Chiesi

Tenedini

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…Targeted capture of specific IRD genes, associated with particular retinal phenotypes, is a strategy being used for molecular diagnosis with increasing frequency. 37–41 Both targeted capture and WES allow for the detection of novel mutations in genes (in contrast to microarrays). Recently targeted capture of known IRD genes in panel-based testing was reportedly more successful than WES, 42 probably due to better coverage of the genes of interest.…”

Section: Discussionmentioning

confidence: 99%

Molecular Diagnosis of Inherited Retinal Diseases in Indigenous African Populations by Whole-Exome Sequencing

Roberts

Ratnapriya

Plessis

et al. 2016

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PurposeA majority of genes associated with inherited retinal diseases (IRDs) have been identified in patients of European origin. Indigenous African populations exhibit rich genomic diversity, and evaluation of reported genetic mutations has yielded low returns so far. Our goal was to perform whole-exome sequencing (WES) to examine variants in known IRD genes in underrepresented African cohorts.MethodsWhole-exome sequencing was performed on 56 samples from 16 families with diverse IRD phenotypes that had remained undiagnosed after screening for known mutations using genotyping-based microarrays (Asper Ophthalmics). Variants in reported IRD genes were identified using WES and validated by Sanger sequencing. Custom TaqMan assays were used to screen for identified mutations in 193 unrelated indigenous Africans with IRDs.ResultsA total of 3494 variants were identified in 217 known IRD genes, leading to the identification of seven different mutations (including six novel) in six genes (RHO, PRPF3, PRPF31, ABCA4, CERKL, and PDE6B) in six distinct families. TaqMan screening in additional probands revealed identical homozygous CERKL and PDE6B variants in four more patients.ConclusionsThis is the first report of WES of patients with IRDs in indigenous African populations. Our study identified genetic defects in almost 40% of the families analyzed, significantly enhancing the molecular diagnosis of IRD in South Africa. Thus, WES of understudied cohorts seems to present an effective strategy for determining novel mutations in heterogeneous retinal diseases.

show abstract

“…The prevalence of IRD in Taiwan remains to be determined, despite the fact that data sourced from the Taiwan National Longitudinal Health Insurance Database and eyeGENE Network (https://eyegene.nih.gov/) have been analysed by several groups. These data reflect inheritance patterns and the prevalence of mutations among patients with RP but not patients with IRD . Lori et al screened medical records from eyeGENE for a total of 170 proband patients with adRP for mutations in 12 disease genes.…”

Section: Introductionmentioning

confidence: 99%

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Chen

Lin

Lee³

et al. 2020

Clinical Exper Ophthalmology

View full text Add to dashboard Cite

Background: Inherited retinal dystrophy (IRD) is a group of irreversible retinal degenerative disorders with significant genotypic and phenotypic heterogeneity, which cause difficulty in making a precise clinical diagnosis.Furthermore, the mutation spectrum of IRD in Taiwan remains unknown. Therefore, our study focused on investigating the spectrum of mutations among Taiwanese families with IRD using targeted exome sequencing (TES) technology. Methods: We recruited a total of 60 unrelated Taiwanese families with IRD; most of them were retinitis pigmentosa. We employed TES to investigate 284 candidate genes. Bioinformatics analysis, Sanger sequencing-based cosegregation testing, and computational assessment were performed to validate each mutation and its pathogenicity. The genotype-phenotype correlation was analysed in all patients with mutations defined in the guidelines provided by the American College of Medical Genetics. Results: We successfully identified genetic causes in 32 families (detection rate of 53.3%). Among them, 16 had a sporadic inheritance (16/36, 44.4%); eight had an autosomal recessive inheritance (8/14, 57.1%); four had an autosomal dominant inheritance (4/5, 80%); four had an X-linked inheritance (4/5, 80%). Among 38 pathological mutations in 19 known genes, 20 mutations are reported here for the first time. Novel mutation spectrum and genotypephenotype correlations were revealed as well. Conclusion: Here we achieved a detection rate of 53.3% and elucidated the mutation spectrum in Taiwanese families with IRD for the first time. The results indicated that CYP4V2 and USH2A might be the most common pathogenic genes in IRD patients in Taiwan. K E Y W O R D Sinherited retinal dystrophy, mutations spectrum, Taiwanese population, targeted exome sequencing

show abstract

NGS-based Molecular diagnosis of 105 eyeGENE® probands with Retinitis Pigmentosa

Cited by 67 publications

References 53 publications

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Unravelling the Complexity of Inherited Retinal Dystrophies Molecular Testing: Added Value of Targeted Next-Generation Sequencing

Molecular Diagnosis of Inherited Retinal Diseases in Indigenous African Populations by Whole-Exome Sequencing

Mutation spectrum and genotype‐phenotype correlation of inherited retinal dystrophy in Taiwan

Contact Info

Product

Resources

About