A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis
AuthorsShah, Rikin K.
Wierenga, Klaas J.
Pokala, Hanumantha R.
Newburger, Peter E.
UMass Chan AffiliationsSchool of Medicine
Senior Scholars Program
Department of Pediatrics, Division of Hematology/Oncology
Department of Biochemistry and Molecular Pharmacology
Document TypeJournal Article
KeywordsCongenital, Hereditary, and Neonatal Diseases and Abnormalities
Hemic and Lymphatic Diseases
MetadataShow full item record
AbstractVPS45-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.
Pediatr Blood Cancer. 2017 Apr 28. doi: 10.1002/pbc.26571. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43549