Clinical and genetic analysis of four patients with congenital neutropenia

Abstract

To delineate the clinical feature and genetic basis of four patients with congenital neutropenia. All patients were subjected to whole exome sequencing (WES). Suspected variants were verified by Sanger sequencing. The patients (two boys and two girls), aged 7 to 15 months, suffered from neutropenia and recurrent infections. Bone marrow smears showed a significant decrease in the proportion of rod-shaped and lobulated granulocytes, which suggested impaired development and maturation of bone marrow neutrophils. WES has discovered heterozygous variants (c.496G>A, c.58C>G, c.391G>A and IVS1+5T>A) of the ELANE gene in the patients. Among these, c.58C>G and IVS1+5T>A were unreported previously. Follow up revealed patients 1 and 3 had periodic neutropenia, while patients 2 and 4 had severe congenital neutropenia. After attaining the definite diagnosis, the patients were treated symptomatically. The main clinical feature of congenital neutropenia is refractory recurrent bacterial infections, for which mutations of the ELANE gene are a common cause. Two novel pathogenic ELANE variants have been discovered in this study.