Familial platelet disorder due to germline exonic deletions in <i>RUNX1</i>: a diagnostic challenge with distinct alterations of the transcript isoform equilibrium.
Marie EngvallYlva KarlssonEkaterina KuchinskayaÅsa JörnegrenLucy MathotTatjana PandzicJosefine PalleViktor LjungströmLucia CavelierEva Hellström LindbergJörg CammengaPanagiotis BaliakasPublished in: Leukemia & lymphoma (2022)
Germline pathogenic variants in <i>RUNX1</i> are associated with familial platelet disorder with predisposition to myeloid malignancies (FPD/MM) with intragenic deletions in <i>RUNX1</i> accounting for almost 7% of all reported variants. We present two new pedigrees with FPD/MM carrying two different germline <i>RUNX1</i> intragenic deletions. The aforementioned deletions encompass exons 1-2 and 9-10 respectively, with the exon 9-10 deletion being previously unreported. RNA sequencing of patients carrying the exon 9-10 deletion revealed a fusion with <i>LINC00160</i> resulting in a change in the 3' sequence of <i>RUNX1</i>. Expression analysis of the transcript isoform demonstrated altered <i>RUNX1a/b/c</i> ratios in carriers from both families compared to controls. Our data provide evidence on the impact of intragenic <i>RUNX1</i> deletions on transcript isoform expression and highlight the importance of routinely performing copy number variant analysis in patients with suspected MM with germline predisposition.
Keyphrases
- copy number
- transcription factor
- mitochondrial dna
- poor prognosis
- dna repair
- single cell
- rna seq
- end stage renal disease
- genome wide
- chronic kidney disease
- ejection fraction
- long non coding rna
- newly diagnosed
- dna methylation
- dendritic cells
- early onset
- cell proliferation
- binding protein
- gene expression
- prognostic factors
- molecular dynamics simulations
- electronic health record
- big data
- amino acid