Spectrum of mutations in congenital neutropenia: a single-centre study in patients of Indian origin.

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 mutations while congenital neutropenia is genetically heterogeneous with mutations in genes like and The presence of 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 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 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 gene for proper characterisation of the genotype.