Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation

被引：11

作者：

van de Vosse, Esther ^{[1
]}

Verhard, Els M. ^{[1
]}

Tool, Anton J. T. ^{[2
]}

de Visser, Adriette W. ^{[1
]}

Kuijpers, Taco W. ^{[2
]}

Hiemstra, Pieter S. ^{[3
]}

van Dissel, Jaap T. ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Infect Dis, NL-2333 ZA Leiden, Netherlands

[2] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands

[3] Leiden Univ, Med Ctr, Dept Pulmonol, NL-2333 ZA Leiden, Netherlands

来源：

ANNALS OF HEMATOLOGY | 2011年 / 90卷 / 02期

关键词：

Severe congenital neutropenia; ELANE; Neutrophil elastase; Mutation; ELA2; COLONY-STIMULATING-FACTOR; FACTOR-RECEPTOR GENE; G-CSF RECEPTOR; ACUTE MYELOID-LEUKEMIA; PATIENT; EXPRESSION; DOMAIN; RISK; PROLIFERATION; RELEVANCE;

D O I：

10.1007/s00277-010-1056-4

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN.

引用

页码：151 / 158

页数：8