A novel RUNX1 exon 3 - 7 deletion causing a familial platelet disorder.

Autor: Almazni I; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK., Chudakou P; Department of Haematology, Lincoln County Hospital, Lincoln, UK., Dawson-Meadows A; Department of Haematology, Lincoln County Hospital, Lincoln, UK., Downes K; East Genomic Laboratory Hub, Cambridge University Hospitals, Cambridge, UK., Freson K; Center for Molecular and Vascular Biology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium., Mason J; West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, UK., Page P; West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, UK., Reay K; West Midlands Regional Genetics Laboratory, Birmingham Women's Hospital, Birmingham, UK., Myers B; Department of Haematology, Lincoln County Hospital, Lincoln, UK.; Department of Haematology, University Hospitals of Leicester, Leicester, UK., Morgan NV; Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Jazyk: angličtina
Zdroj: Platelets [Platelets] 2022 Feb 17; Vol. 33 (2), pp. 320-323. Date of Electronic Publication: 2021 Feb 22.
DOI: 10.1080/09537104.2021.1887470
Abstrakt: 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.
Databáze: MEDLINE
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