Inherited biallelic CSF3R mutations in severe congenital neutropenia


TRIOT A., JAERVINEN P. M. , Arostegui J. I. , MURUGAN D., KOHISTANI N., Dapena Díaz J. L. , ...Daha Fazla

BLOOD, cilt.123, ss.3811-3817, 2014 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 123 Konu: 24
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1182/blood-2013-11-535419
  • Dergi Adı: BLOOD
  • Sayfa Sayıları: ss.3811-3817

Özet

Severe congenital neutropenia (SCN) is characterized by low numbers of peripheral neutrophil granulocytes and a predisposition to life-threatening bacterial infections. We describe a novel genetic SCN type in 2 unrelated families associated with recessively inherited loss-of-function mutations in CSF3R, encoding the granulocyte colony-stimulating factor (G-CSF) receptor. Family A, with 3 affected children, carried a homozygous missense mutation (NM_000760.3:c.922C>T, NP_000751.1:p.Arg308Cys), which resulted in perturbed N-glycosylation and aberrant localization to the cell surface. Family B, with 1 affected infant, carried compound heterozygous deletions provoking frame shifts and premature stop codons(NM_000760.3:c.948_963del, NP_000751.1: p. Gly316fsTer322 and NM_000760.3:c.1245del, NP_000751.1:p.Gly415fsTer432). Despite peripheral SCN, all patients had morphologic evidence of full myeloid cell maturation in bone marrow. None of the patients responded to treatment with recombinant human G-CSF. Our study highlights the genetic and morphologic SCN variability and provides evidence both for functional importance and redundancy of G-CSF receptor-mediated signaling in human granulopoiesis.