A novel homozygous VPS45 p.P468L mutation leading to severe congenital neutropenia with myelofibrosis.
Pediatr Blood Cancer
; 64(9)2017 Sep.
Article
en En
| MEDLINE
| ID: mdl-28453180
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Transporte Vesicular
/
Mielofibrosis Primaria
/
Neutropenia
Tipo de estudio:
Prognostic_studies
Límite:
Female
/
Humans
/
Newborn
Idioma:
En
Revista:
Pediatr Blood Cancer
Asunto de la revista:
HEMATOLOGIA
/
NEOPLASIAS
/
PEDIATRIA
Año:
2017
Tipo del documento:
Article