Severe congenital neutropenia, SRP54 pathogenicity, and a framework for surveillance

Am J Med Genet A. 2023 May;191(5):1434-1441. doi: 10.1002/ajmg.a.63156. Epub 2023 Feb 23.

Abstract

Severe congenital neutropenia (SCN) is a rare disorder, often due to pathogenic variants in genes such as ELANE, HAX1, and SBDS. SRP54 pathogenic variants are associated with SCN and Shwachman-Diamond-like syndrome. Thirty-eight patients with SRP54-related SCN are reported in the literature. We present an infant with SCN, without classic Shwachman-Diamond syndrome features, who presented with recurrent bacterial infections and an SRP54 (c.349_351del) pathogenic variant. Despite ongoing granulocyte colony-stimulating factor therapy, this patient has no evidence of malignant transformation. Here we establish a framework for the future development of universal guidelines to care for this patient population.

Keywords: SRP54; severe congenital neutropenia; surveillance.

Publication types

  • Case Reports

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Congenital Bone Marrow Failure Syndromes / genetics
  • Humans
  • Infant
  • Mutation
  • Neutropenia* / genetics
  • Neutropenia* / pathology
  • Shwachman-Diamond Syndrome
  • Signal Recognition Particle / genetics
  • Virulence

Substances

  • SRP54 protein, human
  • Signal Recognition Particle
  • HAX1 protein, human
  • Adaptor Proteins, Signal Transducing

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3