A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder
Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare inherited disorder confirmed with the presence of a pathogenic germline RUNX1 variant and is thought to be heavily underdiagnosed. RUNX1 has also been found to be mutated in up to 10% of adult AML cases and other cell ma...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2022-02-01
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| Series: | Platelets |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/09537104.2021.1887470 |
| _version_ | 1797684163391782912 |
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| author | Ibrahim Almazni Pavel Chudakou Alison Dawson-Meadows Kate Downes Kathleen Freson Joanne Mason Paula Page Kim Reay Bethan Myers Neil V Morgan |
| author_facet | Ibrahim Almazni Pavel Chudakou Alison Dawson-Meadows Kate Downes Kathleen Freson Joanne Mason Paula Page Kim Reay Bethan Myers Neil V Morgan |
| author_sort | Ibrahim Almazni |
| collection | DOAJ |
| description | Familial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare inherited disorder confirmed with the presence of a pathogenic germline RUNX1 variant and is thought to be heavily underdiagnosed. RUNX1 has also been found to be mutated in up to 10% of adult AML cases and other cell malignancies. We performed targeted next-generation sequencing and subsequent MLPA analysis in a kindred with multiple affected individuals with low platelet counts and a bleeding history. We detected a novel heterozygous exon 3–7 large deletion in the RUNX1 gene in all affected family members which is predicted to remove all of the Runt-homology DNA-binding domain and a portion of the Activation domain. Our results show that the combination of targeted NGS and MLPA analysis is an effective way to detect copy number variants (CNVs) which would be missed by conventional sequencing methods. This precise diagnosis offers the possibility of accurate counseling and clinical management in such patients who could go onto develop other cell malignancies. |
| first_indexed | 2024-03-12T00:25:31Z |
| format | Article |
| id | doaj.art-bf5293d1d2774c9a91b06015384ba76f |
| institution | Directory Open Access Journal |
| issn | 0953-7104 1369-1635 |
| language | English |
| last_indexed | 2024-03-12T00:25:31Z |
| publishDate | 2022-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Platelets |
| spelling | doaj.art-bf5293d1d2774c9a91b06015384ba76f2023-09-15T10:38:09ZengTaylor & Francis GroupPlatelets0953-71041369-16352022-02-0133232032310.1080/09537104.2021.18874701887470A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorderIbrahim Almazni0Pavel Chudakou1Alison Dawson-Meadows2Kate Downes3Kathleen Freson4Joanne Mason5Paula Page6Kim Reay7Bethan Myers8Neil V Morgan9University of BirminghamLincoln County HospitalLincoln County HospitalCambridge University HospitalsUniversity of LeuvenBirmingham Women’s HospitalBirmingham Women’s HospitalBirmingham Women’s HospitalLincoln County HospitalUniversity of BirminghamFamilial Platelet Disorder with associated Myeloid Malignancy (FPDMM) is a rare inherited disorder confirmed with the presence of a pathogenic germline RUNX1 variant and is thought to be heavily underdiagnosed. RUNX1 has also been found to be mutated in up to 10% of adult AML cases and other cell malignancies. We performed targeted next-generation sequencing and subsequent MLPA analysis in a kindred with multiple affected individuals with low platelet counts and a bleeding history. We detected a novel heterozygous exon 3–7 large deletion in the RUNX1 gene in all affected family members which is predicted to remove all of the Runt-homology DNA-binding domain and a portion of the Activation domain. Our results show that the combination of targeted NGS and MLPA analysis is an effective way to detect copy number variants (CNVs) which would be missed by conventional sequencing methods. This precise diagnosis offers the possibility of accurate counseling and clinical management in such patients who could go onto develop other cell malignancies.http://dx.doi.org/10.1080/09537104.2021.1887470bleedingcnvngsplatelet disorderrunx1thrombocytopenia |
| spellingShingle | Ibrahim Almazni Pavel Chudakou Alison Dawson-Meadows Kate Downes Kathleen Freson Joanne Mason Paula Page Kim Reay Bethan Myers Neil V Morgan A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder Platelets bleeding cnv ngs platelet disorder runx1 thrombocytopenia |
| title | A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder |
| title_full | A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder |
| title_fullStr | A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder |
| title_full_unstemmed | A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder |
| title_short | A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder |
| title_sort | novel runx1 exon 3 7 deletion causing a familial platelet disorder |
| topic | bleeding cnv ngs platelet disorder runx1 thrombocytopenia |
| url | http://dx.doi.org/10.1080/09537104.2021.1887470 |
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