Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Karastaneva, A; Nebral, K; Schlagenhauf, A; Baschin, M; Palankar, R; Juch, H; Heitzer, E; Speicher, MR; Höfler, G; Grigorow, I; Urban, C; Benesch, M; Greinacher, A; Haas, OA; Seidel, MG.
Novel phenotypes observed in patients with ETV6-linked leukaemia/familial thrombocytopenia syndrome and a biallelic ARID5B risk allele as leukaemogenic cofactor.
J Med Genet. 2020; 57(6):427-433
Web of Science PubMed FullText FullText_MUG

 

Autor/innen der Med Uni Graz:
Benesch Martin
Heitzer Ellen
Hoefler Gerald
Juch Herbert
Karastaneva Anna
Schlagenhauf Axel
Seidel Markus
Speicher Michael
Urban Ernst-Christian
Altmetrics:

Dimensions Citations:

Plum Analytics:
Abstract:
Background. The phenotypes of patients with the recently discovered, dominant, ETV6-linked leukaemia predisposition and familial thrombocytopenia syndrome are variable, and the exact mechanism of leukaemogenesis remains unclear. Patients and Methods. Here, we present novel clinical and laboratory phenotypes of seven individuals from three families with ETV6 germline mutations and a refined genetic analysis of one child with additional high-hyperdiploid acute lymphoblastic leukaemia (HD-ALL), aiming to elucidate second oncogenic hits. Results. Four individuals from two pedigrees harboured one novel or one previously described variant in the central domain of ETV6 (c.592C>T, p.Gln198* or c.641C>T, p.Pro241Leu, respectively). Neutropenia was an accompanying feature in one of these families that also harboured a variant in RUNX1 (c.1098_1103dup, p.Ile366_Gly367dup), while in the other, an autism-spectrum disorder was observed. In the third family, the index patient suffered from HD-ALL and life-threatening pulmonary mucor mycosis, and had a positive family history of 'immune' thrombocytopenia. Genetic analyses revealed a novel heterozygous mutation in the ETS domain of ETV6 (c.1136T>C, p.Leu379Pro) along with absence of heterozygosity of chromosome (10)(q21.2q21.3), yielding a biallelic leukaemia risk allele in ARID5B (rs7090445-C). The neutrophil function was normal in all individuals tested, and the platelet immune histochemistry of all three pedigrees showed delta-storage-pool defect-like features and cytoskeletal defects. Conclusions. Our clinical observations and results of high-resolution genetic analyses extend the spectrum of possible phenotypes cosegregating with ETV6 germline mutations. Further, we propose ARID5B as potential leukaemogenic cofactor in patients with ETV6-linked leukaemia predisposition and familial thrombocytopenia syndrome. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Find related publications in this database (Keywords)
Immune thrombocytopenia (ITP)
cancer predisposition syndrome (CPS)
high-hyperdiploid acute lymphoblastic leukemia (HD-ALL)
genetic susceptibility to leukemia
delta-storage pool defect
congenital thrombocytopenia
thrombocytopathy syndrome
© Med Uni Graz Impressum