Congenital neutropenia (CN) is a rare inherited hematological disease and its phenotypic, histologic and molecular aspects are heterogeneous. Congenital neutropenia can manifest as isolated neutropenia or neutropenia with extra-hematopoietic abnormalities, immunodeficiency or metabolic diseases and results in recurrent, life-threatening bacterial infections. Mutations in more than 20 genes have been demonstrated to cause CN, some of which cause complex phenotypes.

Usually caused by ELANE mutations although mutations in other genes like HAX-1, G6PC3, and GF11 have also been reported. Identifying the causative mutation aids in the diagnosis and ruling out other secondary causes of neutropenia. In this study we aimed to identify the molecular defects in CN patients by next generation sequencing (NGS).

Next generation sequencing test was performed on peripheral blood specimens of 17 patients diagnosed with congenital or chronic neutropenia and bone marrow failure and hematological malignancy ruled out from January 2021- June 2023. The genes in the NGS panel were; LAMTOR2, CLPB, HAX1, USB1, SBDS, JAGN1, TAZ, ELANE, G6PC3, WAS, CXCR4, GFI1, VPS45, VPS13B.

The median age at presentation of neutropenia was 28.9 months. Mean neutrophil count at diagnosis was 380± 259/mm3. Bone marrow aspiration was performed in ten patients and myeloid maturation arrest was observed five. Granulocyte colony stimulating factor was given for seven patients and all had a response. In the NGS panel TAZ mutation was detected in one patient compatible with Barth Syndrome and VPS13 double heterozygous mutation was detected in one patient compatible with Cohen Syndrome.

Considering the heterogeneity of CN in terms of genotypes and phenotypes expanded next generation sequencing panel would be necessary. The early onset of the disease, clinical severity and associated high risk of malignant transformation in CN strongly suggests the need for early diagnosis and therapeutic intervention.