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

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.

Automated summary

We identified a likely pathogenic variant in NUF2 in a patient with severe microcephaly, congenital bone marrow failure, growth retardation, and renal hypoplasia, which impairs the cell's ability to properly complete mitosis. This finding suggests a unifying causal role of the variant in Fanconi Anaemia, highlighting the unique pathological link between neurogenesis and haematopoiesis.