Various phenotypes of disease associated with mutated DGKE gene

Eur J Med Genet. 2020 Aug;63(8):103953. doi: 10.1016/j.ejmg.2020.103953. Epub 2020 May 13.

Abstract

Atypical haemolytic uraemic syndrome and steroid-resistant nephrotic syndrome are highly rare kidney diseases that can occur in childhood. In some cases, genetic variants may trigger these conditions, although in atypical haemolytic uraemic syndrome they mostly confer only a predisposition to the disease. Most variants causing atypical haemolytic uraemic syndrome were identified in genes encoding proteins regulating the complement pathway; on the other hand, there are approximately 58 genes encoding distinct proteins primarily causing steroid-resistant nephrotic syndrome. We present a child with steroid-resistant nephrotic syndrome and a confirmed homozygous c.966G > A, p.Trp322Ter pathogenic variant in DGKE. This variant was also found in compound with a novel DGKE heterozygous deletion c.171delG, p.Ser58Alafs*111 in a patient from our paediatric cohort with atypical haemolytic uraemic syndrome. Both cases presented with hypertension, nephrotic proteinuria and severe acute kidney injury followed by renal recovery; however, their renal histology was different. In this paper, we deal with the clinical course of children with disrupted DGKE, including the steroid-resistant nephrotic syndrome and atypical haemolytic uraemic syndrome overlap.

Keywords: Atypical haemolytic uraemic syndrome; Children; DGKE nephropathy; Next-generation sequencing; SRNS/aHUS overlap; Steroid-resistant nephrotic syndrome.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Child
  • Diacylglycerol Kinase / genetics*
  • Female
  • Hemolytic-Uremic Syndrome / genetics*
  • Hemolytic-Uremic Syndrome / pathology
  • Homozygote
  • Humans
  • Kidney / pathology
  • Mutation
  • Nephrotic Syndrome / congenital*
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / pathology
  • Phenotype*

Substances

  • DGKE protein, human
  • Diacylglycerol Kinase

Supplementary concepts

  • Nephrotic syndrome, idiopathic, steroid-resistant