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‹ Thu · 16 Apr 2026
Near-term implementable finding

Targeted long-read RNA sequencing for rare disease diagnosis and variant interpretation

A genetic sequencing technique resolved mysterious genetic diagnoses in five previously undiagnosed patients, offering hope for people with rare unexplained diseases.

STRIPE is a targeted long-read RNA-seq strategy that enables deep, full-length transcript sequencing of customized gene panels for rare disease diagnosis, detecting unexpected splice consequences including cryptic intronic polyadenylation from donor splice site variants. Applied to 88 individuals, it resolved variants of uncertain significance and identified pathogenic variants in 5 previously undiagnosed patients, offering a scalable diagnostic tool for the clinical rare disease pipeline.

What the study was

Study design
Targeted long-read RNA-seq validation across two rare disease cohorts
Population
88 individuals spanning two major rare disease groups (mitochondrial disease, congenital disorders of glycosylation and others); Children's Hospital of Philadelphia
Sample size
88
Category
Diagnostics
Maturity
Validated
Journal
Science Advances

Why it surfaced

Novel targeted long-read RNA-seq approach resolves undiagnosed cases in rare disease; clinically scalable and adaptable to any disease-specific gene panel; strong novelty for rare disease diagnostic pipeline.

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