We have located links that may give you full text access.
Targeted long-read sequencing identifies and characterizes structural variants in cases of inherited platelet disorders.
Journal of Thrombosis and Haemostasis : JTH 2023 November 24
BACKGROUND: Genetic diagnosis of inherited platelet disorders (IPD) is mainly performed by high-throughput sequencing (HTS). These short-read-based sequencing methods sometimes fail to characterize the genetics of the disease.
AIMS: To evaluate nanopore long-read DNA sequencing for characterization of structural variants (SVs) in IPD patients.
METHODS: Four patients with a clinical and laboratory diagnosis of Glanzmann thrombasthenia(GT) (P1 and P2) and Hermansky-Pudlak syndrome (HPS) (P3 and P4), in whom HTS missed the underlying molecular cause were included. DNA was analyzed by both standard HTS and nanopore sequencing on a MinION device after enrichment of DNA spanning regions covering GT and HPS genes.
RESULTS: In the GT patients, HTS identified only one heterozygous ITGB3 splice variant c.2301+1G>C in P2. In the HPS patients, a homozygous deletion in HPS5 was suspected in P3 and two heterozygous HPS3 variants, c.2464C>T (p.Arg822*) and a deletion affecting 2 exons were reported in P4. Nanopore sequencing revealed a complex SV affecting exons 2-6 in ITGB3 (deletion-inversion-duplication) in homozygosity in P1 and in compound heterozygosity with the splice variant in P2. In the two HPS patients, nanopore defined the length of the SVs, which were characterized at nucleotide resolution. This allowed the identification of repetitive Alu elements at the breakpoints and the design of specific PCRs for family screening.
CONCLUSIONS: The nanopore technology overcomes the limitations of standard short-read sequencing techniques in SV characterization. Using nanopore we characterized novel defects in ITGB3, HPS5 and HPS3, highlighting the utility of long-read sequencing as an additional diagnostic tool in IPD.
AIMS: To evaluate nanopore long-read DNA sequencing for characterization of structural variants (SVs) in IPD patients.
METHODS: Four patients with a clinical and laboratory diagnosis of Glanzmann thrombasthenia(GT) (P1 and P2) and Hermansky-Pudlak syndrome (HPS) (P3 and P4), in whom HTS missed the underlying molecular cause were included. DNA was analyzed by both standard HTS and nanopore sequencing on a MinION device after enrichment of DNA spanning regions covering GT and HPS genes.
RESULTS: In the GT patients, HTS identified only one heterozygous ITGB3 splice variant c.2301+1G>C in P2. In the HPS patients, a homozygous deletion in HPS5 was suspected in P3 and two heterozygous HPS3 variants, c.2464C>T (p.Arg822*) and a deletion affecting 2 exons were reported in P4. Nanopore sequencing revealed a complex SV affecting exons 2-6 in ITGB3 (deletion-inversion-duplication) in homozygosity in P1 and in compound heterozygosity with the splice variant in P2. In the two HPS patients, nanopore defined the length of the SVs, which were characterized at nucleotide resolution. This allowed the identification of repetitive Alu elements at the breakpoints and the design of specific PCRs for family screening.
CONCLUSIONS: The nanopore technology overcomes the limitations of standard short-read sequencing techniques in SV characterization. Using nanopore we characterized novel defects in ITGB3, HPS5 and HPS3, highlighting the utility of long-read sequencing as an additional diagnostic tool in IPD.
Full text links
Related Resources
Trending Papers
Advances in Clinical Cardiology 2023: A Summary of Key Clinical Trials.Advances in Therapy 2024 May 15
Nutrition in the intensive care unit: from the acute phase to beyond.Intensive Care Medicine 2024 May 22
The Therapy and Management of Heart Failure with Preserved Ejection Fraction: New Insights on Treatment.Cardiac Failure Review 2024
Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes.Cochrane Database of Systematic Reviews 2024 May 22
Bronchiectasis management in adults: state of the art and future directions.European Respiratory Journal 2024 May 24
Drug Therapy for Acute and Chronic Heart Failure with Preserved Ejection Fraction with Hypertension: A State-of-the-Art Review.American Journal of Cardiovascular Drugs : Drugs, Devices, and Other Interventions 2024 April 5
Pathophysiological Link and Treatment Implication of Heart Failure and Preserved Ejection Fraction in Patients with Chronic Kidney Disease.Biomedicines 2024 April 31
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app
All material on this website is protected by copyright, Copyright © 1994-2024 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.
By using this service, you agree to our terms of use and privacy policy.
Your Privacy Choices
You can now claim free CME credits for this literature searchClaim now
Get seemless 1-tap access through your institution/university
For the best experience, use the Read mobile app