De novo NUF2 variant in a novel inherited bone marrow failure syndrome including microcephaly and renal hypoplasia

Br J Haematol. 2022 Dec;199(5):739-743. doi: 10.1111/bjh.18461. Epub 2022 Sep 16.

Abstract

In a patient with severe microcephaly, congenital bone marrow failure, growth retardation, and renal hypoplasia, we identified a likely pathogenic variant in NUF2 that impairs the cell's ability to properly complete mitosis. Interestingly, these clinical features as well as the observed cellular alterations are highly reminiscent of what is reported in Fanconi Anaemia supporting a unifying causal role of the variant in the disease. This case provides the first evidence that a kinetochore defect, previously associated with microcephaly, can be responsible for an inherited bone marrow failure syndrome, highlighting the unique pathological link between neurogenesis and haematopoiesis.

Keywords: bone marrow failure; development; genetic disorders; molecular genetics.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins
  • Congenital Bone Marrow Failure Syndromes
  • Fanconi Anemia*
  • Humans
  • Microcephaly* / genetics

Substances

  • Cell Cycle Proteins
  • NUF2 protein, human