Resolving the diagnostic odyssey in inherited retinal dystrophies through long-read genome sequencing DOI Creative Commons
Gerardo Fabian-Morales, Vianey Ordóñez-Labastida, William J. Rowell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

ABSTRACT Background Inherited Retinal Dystrophies (IRDs) are visually disabling monogenic diseases with remarkable genetic and phenotypic heterogeneity. Mutations in more than 300 different genes have been identified as disease causing. Genetic diagnosis of IRDs has greatly improved thanks to the incorporation Next Generation Sequencing (NGS) approaches. However, current IRD molecular yield using NGS is approximately 60% negative cases can be explained by variants that not usually widely used short reads-NGS such structural (SVs) or located uncovered, low complexity, repetitive, highly homologous, GC-rich regions. Long-read genome sequencing (LR-GS) an emerging technology produces 10-20 kb reads expected overcome short-read limitations clinical context, thus improving diagnostic heterogeneous IRDs. Objective To describe LR-GS utility 3 unrelated, previously unsolved cases. Material & Methods was performed on probands previous inconclusive testing (either exome gene panel sequencing). Whole libraries were prepared SMRTbell® prep kit. PacBio Revio system. Results A definite established homozygous deep intronic variant c.4885+740A>T USH2A a proband Usher syndrome; intragenic deletion involving EYS exon 24 found Retinitis pigmentosa. Finally, syndrome compound heterozygous for multiexonic duplication exons 22-32. Conclusion Our case series show efficiency setting detect disease-causing missed techniques, rate genetically

Language: Английский

Nanopore sequencing: flourishing in its teenage years DOI
Tianyuan Zhang, Hanzhou Li, Mian Jiang

et al.

Journal of genetics and genomics/Journal of Genetics and Genomics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 1, 2024

Language: Английский

Citations

18
Genetics and diagnostics of inherited retinal diseases in the era of whole genome sequencing DOI Creative Commons
Heidi Stöhr, Bernhard H. F. Weber

Medizinische Genetik, Journal Year: 2025, Volume and Issue: 37(1), P. 3 - 10

Published: Feb. 6, 2025

Language: Английский

Citations

0
Long-Read Whole-Genome Sequencing as a Tool for Variant Detection in Inherited Retinal Dystrophies DOI Open Access

Cristina Rodilla,

Gonzalo Núñez‐Moreno, Yolanda Benitez

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3825 - 3825

Published: April 18, 2025

Advances in whole-genome sequencing (WGS) have significantly enhanced our ability to detect genomic variants underlying inherited diseases. In this study, we performed long-read WGS on 24 patients with retinal dystrophies (IRDs) validate the utility of nanopore detecting variations. We confirmed presence all previously detected and demonstrated that approach allows for precise refinement structural (SVs). Furthermore, could perform genotype phasing by only probands, confirming were trans. Moreover, enables detection complex variants, such as transposon insertions rearrangements. This comprehensive assessment illustrates power capturing diverse forms variation improving diagnostic accuracy IRDs.

Language: Английский

Citations

0
Long-read technologies identify a hidden LINE-1/ERV1 insertion in IQCB1 as causative variant for Senior-Løken syndrome DOI Creative Commons
Suzanne E. de Bruijn, L. Ingeborgh van den Born, Ronny Derks

et al.

npj Genomic Medicine, Journal Year: 2025, Volume and Issue: 10(1)

Published: April 22, 2025

Language: Английский

Citations

0
Resolving the diagnostic odyssey in inherited retinal dystrophies through long-read genome sequencing DOI Creative Commons
Gerardo Fabian-Morales, Vianey Ordóñez-Labastida, William J. Rowell

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 30, 2024

ABSTRACT Background Inherited Retinal Dystrophies (IRDs) are visually disabling monogenic diseases with remarkable genetic and phenotypic heterogeneity. Mutations in more than 300 different genes have been identified as disease causing. Genetic diagnosis of IRDs has greatly improved thanks to the incorporation Next Generation Sequencing (NGS) approaches. However, current IRD molecular yield using NGS is approximately 60% negative cases can be explained by variants that not usually widely used short reads-NGS such structural (SVs) or located uncovered, low complexity, repetitive, highly homologous, GC-rich regions. Long-read genome sequencing (LR-GS) an emerging technology produces 10-20 kb reads expected overcome short-read limitations clinical context, thus improving diagnostic heterogeneous IRDs. Objective To describe LR-GS utility 3 unrelated, previously unsolved cases. Material & Methods was performed on probands previous inconclusive testing (either exome gene panel sequencing). Whole libraries were prepared SMRTbell® prep kit. PacBio Revio system. Results A definite established homozygous deep intronic variant c.4885+740A>T USH2A a proband Usher syndrome; intragenic deletion involving EYS exon 24 found Retinitis pigmentosa. Finally, syndrome compound heterozygous for multiexonic duplication exons 22-32. Conclusion Our case series show efficiency setting detect disease-causing missed techniques, rate genetically

Language: Английский

Citations

0