A novel MPIG6B gene mutation in an adolescent girl with congenital thrombocytopenia and myelofibrosis

The MPIG6B gene, which encodes G6b-B, regulates platelet production, aggregation, and activation. Loss-of-function of G6b-B can cause thrombocytopenia, myelofibrosis, and anemia in both humans and mice. Several pathogenic MPIG6B mutations have been reported, such as c.324C>A (p.C108*), c.61_61+1dup (p.Ala21GlyfsX159), c.149dup (p.Ala52GlyfsX128), G6b c.469G>A (p.Gly157Arg) c.392delC (p.P134Lfs*10), and c523C>T(p.Arg175Ter). We have added to this database by reporting a new homozygous nonsense mutation (c.420T>A(p.Tyr140Ter)) of MPIG6B in a 14-year-old girl who presented with pallor, scattered cutaneous petechia of the limb, thrombocytopenia, anemia and myelofibrosis. This novel MPIG6B gene mutation encodes a shorter mutated G6b-B that does contain the transmembrane region immunoreceptor tyrosine-based inhibitory motif. The patient was effectively treated with allogeneic hematopoietic stem cell transplantation with peripheral stem cells from a matched unrelated donor. Her symptoms and the MPIG6B mutation disappeared after treatment, and she was healthy and had returned to school at the last follow-up.