A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis
Authors
Shah, Rikin K.Munson, Mary
Wierenga, Klaas J.
Pokala, Hanumantha R.
Newburger, Peter E.
Crawford, David
UMass Chan Affiliations
School of MedicineSenior Scholars Program
Department of Pediatrics, Division of Hematology/Oncology
Department of Biochemistry and Molecular Pharmacology
Document Type
Journal ArticlePublication Date
2017-04-28Keywords
Congenital, Hereditary, and Neonatal Diseases and AbnormalitiesHematology
Hemic and Lymphatic Diseases
Oncology
Pediatrics
Metadata
Show full item recordAbstract
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.Source
Pediatr Blood Cancer. 2017 Apr 28. doi: 10.1002/pbc.26571. Link to article on publisher's site
DOI
10.1002/pbc.26571Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43549PubMed ID
28453180Related Resources
ae974a485f413a2113503eed53cd6c53
10.1002/pbc.26571