Informace o publikaci
ANALYSIS OF ANKRD26 GENE 5'UTR VARIANTS IN A COHORT OF CZECH PATIENTS WITH SUSPECTED HEREDITARY HEMATOLOGICAL DISORDER
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Konferenční abstrakty |
| Fakulta / Pracoviště MU | |
| Citace | |
| Popis | Background: VVariants in the 5‘UTR region c.-116C - c.-140C of ANKRD26 gene were described as causal for ANKRD26-related thrombocytopenia (THC2). This autosomal dominant disorder presents as mild to moderate thrombocytopenia with minimal symptoms but for the carrier means increased risk of malignancy, mainly myeloproliferation. Recently, the c.-140C>G variant was described in dbSNP in 6.2% non-Finnish European population. Aims: This fact raises the question whether the ANKDR26 c.-140C>G variant is a pathogenic mutation responsible for the THC2 phenotype or, given its frequency, a population polymorphism. Methods: Exome sequencing (WES) was performed on a cohort of patients with suspected inherited hematological disorder. WES results were confirmed by Sanger sequencing. Subsequently, the cohort of patients with a variant in 5’UTR in ANKRD26 gene was analyzed with respect to clinical symptoms. Finally, variants in the 5’UTR of ANKRD26 gene were searched in the genomes of the healthy Czech population. Results: WES analysis was performed on the cohort of 53 patients from 31 families with following results: 12 individuals from 5 families carry heterozygous, 1 homozygous c.-140C>G variant, and 3 individuals from 1 family heterozygous c.- 118C>T variant of ANKRD26 gene. No other gene variant was detected that was causal for their phenotype except for that found in the 5’UTR of ANKRD26 gene. The c.-118C>T variant was already published by several authors and was always associated with thrombocytopenia. From clinical data: Thrombocytopenia was present in 4 individuals: 1 with c.- 140C>G variant and 3 with c.-118C>T variant. Moreover, 3 individuals with c.-140C>G variant were diagnosed with the oncologic disorder: 2 with essential thrombocythemia and 1 with multiple myeloma. Aggregation test results were available from 9 individuals from 4 families with c.-140C>G variant: 5 individuals showed platelet hypoaggregation after Collagen, ADP, and Epinephrine – Table 1. Besides, one individual showed hypoaggregation similar to von Willebrand disease IIB. Analysis of 176 healthy Czech individuals showed presence of only one 5’UTR ANKDR26 variant: c.- 140C>G in 21 individuals (11.9%). Summary/Conclusion: We can conclude that most individuals in our cohort (7 out of 9) with the c.-140C>G variant in the 5’UTR of ANKRD26 gene show pathology in platelet aggregation, but only one of them has thrombocytopenia. In addition, three individuals with this gene variant developed malignancy. To answer the above question, whether the ANKRD26 c.-140C>G variant is pathogenic or population polymorphism, functional analysis of this variant must be performed. Our current data show that the ANKRD26 c.-140C>G variant is probably not that pathogenic, as was published. |