Title

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

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Department of Pediatrics, Division of Hematology/Oncology; Senior Scholars Program; School of Medicine

Publication Date

2017-04-28

Document Type

Article

Disciplines

Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Hematology | Hemic and Lymphatic Diseases | Oncology | Pediatrics

Abstract

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.

DOI of Published Version

10.1002/pbc.26571

Source

Pediatr Blood Cancer. 2017 Apr 28. doi: 10.1002/pbc.26571. Link to article on publisher's site

Journal/Book/Conference Title

Pediatric blood and cancer

Related Resources

Link to Article in PubMed

PubMed ID

28453180

Share

COinS