Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients.
PMID 30792900 | PMCID PMC6375963 | DOI 10.1038/s41525-019-0079-6 · NPJ genomic medicine · 2019
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | ITGA2B | “Around 490 mutations in ITGA2B and ITGB3 genes were reported.” | 0.98 | hgnc_dict_v1 |
| gene | ITGB3 | “Around 490 mutations in ITGA2B and ITGB3 genes were reported.” | 0.98 | hgnc_dict_v1 |
| gene | ITGA2 | “In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8.” | 0.98 | hgnc_dict_v1 |
| gene | VWF | “In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8.” | 0.98 | hgnc_dict_v1 |
| gene | F8 | “In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8.” | 0.98 | hgnc_dict_v1 |
| population | Population | “We screened 72 individuals (including unaffected family members) using a panel of 393 genes (SHGP heme panel).” | 0.80 | saudi_context_rules_v1 |