title: Early-Onset Juvenile SLE Associated With a Novel Mutation in Protein Kinase C δ.
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.
authors.affiliation: Infection, Inflammation, and Rheumatology Section, Infection, Immunity, Inflammation and Physiological Medicine Programme, UCL Institute of Child Health, London, United Kingdom; s.nanthapisal@ucl.ac.uk.
authors.forename: Sira
authors.initials: S
authors.lastname: Nanthapisal
authors.affiliation: Infection, Inflammation, and Rheumatology Section, Infection, Immunity, Inflammation and Physiological Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Ebun
authors.initials: E
authors.lastname: Omoyinmi
authors.affiliation: Infection, Inflammation, and Rheumatology Section, Infection, Immunity, Inflammation and Physiological Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Murphy
authors.affiliation: Infection, Inflammation, and Rheumatology Section, Infection, Immunity, Inflammation and Physiological Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Ariane
authors.initials: A
authors.lastname: Standing
authors.affiliation: Luton & Dunstable University Hospital NHS Foundation Trust, Luton, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Eisenhut
authors.affiliation: Infection, Inflammation, and Rheumatology Section, Infection, Immunity, Inflammation and Physiological Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Despina
authors.initials: D
authors.lastname: Eleftheriou
authors.affiliation: Infection, Inflammation, and Rheumatology Section, Infection, Immunity, Inflammation and Physiological Medicine Programme, UCL Institute of Child Health, London, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Brogan
mesh_terms: D002675:Child, Preschool; D003241:Consanguinity; D004252:DNA Mutational Analysis; D003937:Diagnosis, Differential; D019066:Facies; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D006720:Homozygote; D006801:Humans; D007223:Infant; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D010375:Pedigree; D051745:Protein Kinase C-delta / Q000235:genetics*; D000069283:Rituximab / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000069283:Rituximab; D051745:Protein Kinase C-delta