Early-Onset Juvenile SLE Associated With a Novel Mutation in Protein Kinase C δ

Pediatrics. 2017 Jan;139(1):e20160781. doi: 10.1542/peds.2016-0781. Epub 2016 Dec 21.

Abstract

Juvenile systemic lupus erythematosus (jSLE) is rare before 5 years of age. Monogenic causes are suspected in cases of very early onset jSLE particularly in the context of a family history and/or consanguinity. We performed whole-exome sequencing and homozygosity mapping in the siblings presented with early-onset jSLE. A novel homozygous missense mutation in protein kinase C delta (c.1294G>T; p.Gly432Trp) was identified in both patients. One patient showed a marked clinical response and resolution inflammation with rituximab therapy. This report demonstrates the clinical importance of identifying monogenic causes of rare disease to provide a definitive diagnosis, help rationalize treatment, and facilitate genetic counseling.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child, Preschool
  • Consanguinity
  • DNA Mutational Analysis*
  • Diagnosis, Differential
  • Facies
  • Female
  • Follow-Up Studies
  • Genetic Carrier Screening
  • Genetic Testing
  • Homozygote
  • Humans
  • Infant
  • Lupus Erythematosus, Systemic / diagnosis*
  • Lupus Erythematosus, Systemic / drug therapy
  • Lupus Erythematosus, Systemic / genetics*
  • Male
  • Pedigree
  • Protein Kinase C-delta / genetics*
  • Rituximab / therapeutic use
  • Treatment Outcome

Substances

  • Rituximab
  • Protein Kinase C-delta