A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis

作者：Shah Rikin K; Munson Mary; Wierenga Klaas J; Pokala Hanumantha R; Newburger Peter E; Crawford David^*

来源：Pediatric Blood and Cancer, 2017, 64(9): e26571.

DOI：10.1002/pbc.26571

• primary myelofibrosis of infancy
• severe congenital neutropenia
• SNARE
• VPS45

VPS45-associated severe congenital neutropenia (SCN) is a rare disorder characterized by life-threating infections, neutropenia, neutrophil and platelet dysfunction, poor response to filgrastim, and myelofibrosis with extramedullary hematopoiesis. We present a patient with SCN due to a homozygous c.1403C>T (p.P468L) mutation in VPS45, critical regulator of SNARE-dependent membrane fusion. Structural modeling indicates that P468, like the T224 and E238 residues affected by previously reported mutations, cluster in a VPS45 "hinge" region, indicating its critical role in membrane fusion and VPS45-associated SCN. Bone marrow transplantation, complicated by early graft failure rescued with stem cell boost, led to resolution of the hematopoietic phenotype.

• 出版日期2017-9