Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients

NPJ Genomic Medicine
Tarek OwaidahNada Al Tassan

Abstract

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder. Around 490 mutations in ITGA2B and ITGB3 genes were reported. We aimed to use targeted next-generation sequencing (NGS) to identify variants in patients with GT. We screened 72 individuals (including unaffected family members) using a panel of 393 genes (SHGP heme panel). Validation was done by Sanger sequencing and pathogenicity was predicted using multiple tools. In 83.5% of our cohort, 17 mutations were identified in ITGA2B and ITGB3 (including 6 that were not previously reported). In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8. The SHGP heme panel can be used as a high-throughput molecular diagnostic assay to screen for mutations and variants in GT cases and carriers. Our findings expand the molecular landscape of GT and emphasize the robustness and usefulness of this panel.

References

Dec 1, 1993·Journal of Clinical Pathology·R Nounou, D Spence
Mar 10, 2006·Thrombosis and Haemostasis·Patrizia NorisCarlo L Balduini
May 1, 1996·Annals of Saudi Medicine·I M Al-FawazM S Harakati
Aug 15, 2009·American Journal of Human Genetics·Tracy TuckerJan M Friedman
Nov 14, 2012·Expert Review of Hematology·Alan T NurdenPaquita Nurden
Aug 10, 2013·Seminars in Thrombosis and Hemostasis·Alan T NurdenDavid A Wilcox
Mar 17, 2015·Human Mutation·Yu SunGijs W E Santen
Apr 2, 2015·Proceedings of the National Academy of Sciences of the United States of America·Lorena BuitragoBarry S Coller
Feb 18, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·J M BastidaJ R González-Porras
Feb 19, 2016·Journal of Cardiovascular Translational Research·Chee Jian PuaStuart A Cook
Feb 27, 2016·The Journal of Allergy and Clinical Immunology·Hamoud Al-MousaAbbas Hawwari
Apr 21, 2016·Blood·Claire LentaigneUNKNOWN BRIDGE-BPD Consortium and the ThromboGenomics Consortium
Sep 15, 2016·Scientific Reports·Matthew CarriganG Jane Farrar
Jul 19, 2017·BMC Bioinformatics·John AlexanderPeristera Paschou

❮ Previous
Next ❯

Citations

May 2, 2020·Haemophilia : the Official Journal of the World Federation of Hemophilia·Tarek Owaidah
Jul 17, 2021·Indian Journal of Hematology & Blood Transfusion : an Official Journal of Indian Society of Hematology and Blood Transfusion·Ritika SharmaReena Das
Jul 18, 2021·NPJ Genomic Medicine·Batoul BazNada Al Tassan

❮ Previous
Next ❯

Methods Mentioned

BETA
exome sequencing
PCR

Software Mentioned

PredictSNP2
Torrent Suite Variant Caller
CADD
Combined Annotation Depletion ( CADD )
ANNOVAR
Ion Torrent Suite
Variant Ranker

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.