AB1275 SUGGESTED APPROACH TO UBA1 GENE MUTATION TESTING IN PATIENTS WITH SUSPECTED VEXAS SYNDROME
| Autor: | K. Pavelcova, B. Stiburkova, V. Balajková, M. Belickova, C. Salek, M. Vostry, H. Mann, J. Vencovský |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Annals of the Rheumatic Diseases. 81:1745.2-1745 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | BackgroundVEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently identified autoinflammatory disease caused by de novo somatic mutations in the X-linked gene UBA1 (1). This disease is clinically characterized by inflammatory symptoms and bone marrow failure (2).ObjectivesThe aim of our study was to identify genetic variants associated with VEXAS syndrome and to design an algorithm for detection of UBA1 gene mutations in patients with suspected VEXAS syndrome, which could be used for diagnosis.MethodsWe examined the UBA1 gene in 9 patients with clinically suspected VEXAS syndrome. We first focused on variants p.Met41Val, p.Met41Thr and p.Met41Leu with a known association with this disease (1). Samples of individual blood cell populations obtained by magnetic isolation were evaluated using RFLP, tetra-primer ARMS-PCR and Sanger sequencing. Subsequently, we analyzed the remaining exons of the UBA1 gene by Sanger sequencing.ResultsUsing the above described method we have identified the previously described variants p.Met41Thr in two and p.Met41Leu in another two patients. In one patient, we discovered a new mutation p.Gly477Ala (c.1430G>C) in exon 14 that has not yet been identified. The presence of these variants and their allelic forms (heterozygous / homozygous) varied between cell populations in individual patients.ConclusionThe increasing number of reports suggests that VEXAS syndrome is not rare. In patients with clinical suspicion, typically UBA1 sequencing analysis of haematopoietic cells is performed in hot spot sites of p.Met41 in exon 3 only. Our results suggest that other variants, such as the newly identified p.Gly477Ala variant, may also be associated with clinical features of VEXAS syndrome. We propose that an extended analysis of all coding regions of the UBA1 gene may uncover other mutations with putative functional consequences.References[1]Beck DB, et al. Somatic Mutations in UBA1 and Severe Adult-Onset Autoinflammatory Disease. N Engl J Med. 2020 Dec 31;383(27):2628-2638. doi: 10.1056/NEJMoa2026834.[2]Grayson PC, et al. VEXAS syndrome. Blood. 2021 Jul 1;137(26):3591-3594. doi: 10.1182/blood.2021011455.AcknowledgementsSupported by MH CZ: DRO (Institute of Rheumatology, 00023728), RVO (VFN, 64165), DRO (IHBT, 00023736), grant NV18-03-00227, and grant NU21-05-00522.Disclosure of InterestsNone declared |
| Databáze: | OpenAIRE |
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