Congenital thrombocytopenia associated with a heterozygous variant in the MEIS1 gene encoding a transcription factor essential for megakaryopoiesis

Abstract

The transcription factor MEIS1 (myeloid ectotrophic insertion site 1) is crucial for the maintenance of hematopoietic stem cells and for megakaryopoiesis. Germline variants in MEIS1 are associated with restless-leg syndrome, but were not previously shown to cause cytopenias. This is the first report of a patient with congenital thrombocytopenia associated with a sequence variant in MEIS1, presenting with early onset severe thrombocytopenia and mild signs of bone marrow stress. Whole exome sequencing revealed a de novo monoallelic splice site variant in MEIS1, NM_002398.3:exon4:c.432 + 5 G > C, leading to a premature stop codon. We propose that heterozygous mutations in MEIS1 may cause congenital thrombocytopenia.

Keywords:

• Congenital
• MEIS1
• thrombocytopenia

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

NO, LBS – performed genetic analyses and counseling.

TK, SNL, NM, OD - performed functional studies.

OSS, OG, JY, ES, HT - provided clinical care for the patient.

HT, OSS - wrote the manuscript.

HT, LBS, OSS, NO - initiated the study.

Supplementary material

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Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.