MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia

Germeshausen M, Ancliff P, Estrada J, Metzler M, Ponstingl E, Ruetschle H, Schwabe D, Scott RH, Unal S, Wawer A, Zeller B, Ballmaier M (2018)

Publication Type: Journal article

Publication year: 2018

Journal

Blood Advances American Society of Hematology

Book Volume: 2

Pages Range: 586-596

Journal Issue: 6

DOI: 10.1182/bloodadvances.2018016501

Abstract

Heterozygous mutations in MECOM (MDS1 and EVI1 complex locus) have been reported to be causative of a rare association of congenital amegakaryocytic thrombocytopenia and radioulnar synostosis. Here we report on 12 patients with congenital hypomegakaryocytic thrombocytopenia caused by MECOM mutations (including 10 novel mutations). The mutations affected different functional domains of the EVI1 protein. The spectrum of phenotypes was much broader than initially reported for the first 3 patients; we found familial as well as sporadic cases, and the clinical spectrum ranged from isolated radioulnar synostosis with no or mild hematological involvement to severe bone marrow failure without obvious skeletal abnormality. The clinical picture included radioulnar synostosis, bone marrow failure, clinodactyly, cardiac and renal malformations, B-cell deficiency, and presenile hearing loss. No single clinical manifestation was detected in all patients affected by MECOM mutations. Radioulnar synostosis and B-cell deficiency were observed only in patients with mutations affecting a short region in the C-terminal zinc finger domain of EVI1. We propose the term MECOM-associated syndrome for this heterogeneous hereditary disease and inclusion of MECOM sequencing in the diagnostic workup of congenital bone marrow failure.

Authors with CRIS profile

Markus Metzler Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School DE Germany (DE) Technische Universität München (TUM) DE Germany (DE) Great Ormond Street Hospital (GOSH) GB United Kingdom (GB) Methodist Healthcare System of San Antonio, LTD., L.L.P. DE Germany (DE) Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet NO Norway (NO) Hacettepe University TR Turkey (TR) Universitätsklinikum Frankfurt am Main (KGU) DE Germany (DE)

How to cite

APA:

Germeshausen, M., Ancliff, P., Estrada, J., Metzler, M., Ponstingl, E., Ruetschle, H.,... Ballmaier, M. (2018). MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia. Blood Advances, 2(6), 586-596. https://dx.doi.org/10.1182/bloodadvances.2018016501

MLA:

Germeshausen, Manuela, et al. "MECOM-associated syndrome: a heterogeneous inherited bone marrow failure syndrome with amegakaryocytic thrombocytopenia." Blood Advances 2.6 (2018): 586-596.

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