Clinical and molecular characteristics of Thai patients with ELANE- related neutropaenia

J Clin Pathol. 2022 Feb;75(2):99-103. doi: 10.1136/jclinpath-2020-207139. Epub 2020 Dec 14.

Abstract

Aims: Congenital neutropaenia is a rare inherited disorder that mainly affects neutrophils causing severe infection. Mutations in several genes have been implicated in the disease pathogenesis. The genetic defects may vary in different populations, influenced by ethnicity and geographical location. Here we describe the clinical and genotypic characteristics of seven unrelated Thai cases with congenital neutropaenia.

Methods: Seven unrelated patients with congenital neutropaenia were enrolled (5 female and 2 male) at King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Clinical and laboratory data were collected. Whole exome sequencing (WES) analysis was performed in all cases.

Results: WES successfully identified disease-causing mutations in the ELANE gene in all cases, including two novel ones: a heterozygous 12 base pair (bp) inframe insertion (c.289_300dupCAGGTGTTCGCC; p.Q97_A100dup) and a heterozygous 18 bp inframe deletion (c.698_715delCCCCGGTGGCACAGTTTG; p.A233_F238delAPVAQF). Five other previously described ELANE mutations (p.Arg103Pro, p.Gly214Arg, p.Trp241X, p.Ser126Leu and p.Leu47Arg) were also detected.

Conclusions: All Thai patients with congenital neutropaenia in this study harboured causative mutations in the ELANE gene, suggesting it the most common associated with the disease. Two novel mutations were also identified, expanding the genotypic spectrum of ELANE.

Keywords: diseases; genetics; haematological diseases; infant; leucocytes; newborn.

MeSH terms

  • Child
  • Child, Preschool
  • Congenital Bone Marrow Failure Syndromes / diagnosis
  • Congenital Bone Marrow Failure Syndromes / drug therapy
  • Congenital Bone Marrow Failure Syndromes / genetics*
  • DNA Mutational Analysis
  • Exome Sequencing
  • Female
  • Genetic Predisposition to Disease
  • Granulocyte Colony-Stimulating Factor / therapeutic use
  • Humans
  • Infant
  • Leukocyte Elastase / genetics*
  • Male
  • Mutation*
  • Neutropenia / congenital*
  • Neutropenia / diagnosis
  • Neutropenia / drug therapy
  • Neutropenia / genetics
  • Phenotype
  • Thailand
  • Treatment Outcome
  • Young Adult

Substances

  • Granulocyte Colony-Stimulating Factor
  • ELANE protein, human
  • Leukocyte Elastase

Supplementary concepts

  • Neutropenia, Severe Congenital, Autosomal Recessive 3