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

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.

journal_name

Pediatr Blood Cancer

journal_title

Pediatric blood & cancer

authors

Shah RK,Munson M,Wierenga KJ,Pokala HR,Newburger PE,Crawford D

doi

10.1002/pbc.26571

subject

Has Abstract

pub_date

2017-09-01 00:00:00

issue

9

eissn

1545-5009

issn

1545-5017

journal_volume

64

pub_type

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