Aims Congenital and cyclical neutropenia are rare inherited diseases that result in recurrent life-threatening bacterial infections due to a deficiency of mature neutrophils. Cyclical neutropenia is usually caused by heterozygous ELANE mutations while congenital neutropenia is genetically heterogeneous with mutations in genes like ELANE, HAX-1, G6PC3 and GFI1. The presence of ELANE mutation aids in the establishment of diagnosis and rules out other secondary causes of neutropenia such as autoimmune cytopenia and evolving aplasia. Further, patients with ELANE mutations are also at a high risk of developing myelodysplasia or acute myeloid leukaemia. Hence it is important to screen for these mutations in patients presenting with neutropenia early in life.
Methods The study included 52 patients who were evaluated for inherited neutropenia. Genomic DNA was extracted from peripheral blood leucocytes and mutation analysis was done by bidirectional Sanger sequencing.
Results Ten different missense, frameshift or splice site variants in ELANE gene were identified in 11 patients: c.125C>T (p.Pro42Leu), c.164G>A (p.Cys55Tyr), c.169G>A (p.Ala57Thr), c.179T>C (p.Ile60Thr), c.770C>T (p.Pro257Leu), c.367–8C>A, c.597+1G>A along with three novel mutations c.302T>A (p.Val101Glu), c.468G>T (p.Try156Cys) and c.596delT (Phe199Ser fs*13). Family studies were available for three patients and, in all three instances, the mutation had a de novo origin.
Conclusion The widespread distribution of mutations suggests the need to screen all the exons in ELANE gene for proper characterisation of the genotype.
- de novo
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Handling editor Mary Frances McMullin.
Contributors AKA: conceptual development of the study, performed the research, collected and analysed the data, wrote the paper. SA, HS: performed the molecular analysis. ESE: provided the laboratory inputs and reviewed the paper. AK, FNA: provided the clinical inputs. BG, VM: provided the clinical inputs and reviewed the paper. PB: conceptual development of the study, performed research, analysed the data, wrote and reviewed the paper.
Funding This study was supported by grant BT/MB/ 04/2004 from the Department of Biotechnology, Government of India.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement Not applicable.