Juvenile arthritis caused by a novel FAMIN (LACC1) mutation in two children with systemic and extended oligoarticular course

  • Pediatr Rheumatol Online J. 2016 Nov 24;14(1):63. doi: 10.1186/s12969-016-0124-2.
Tilmann Kallinich  1  2 ,  Anne Thorwarth  3  4 ,  Sae-Lim von Stuckrad  3  4 ,  Angela Rösen-Wolff  5 ,  Hella Luksch  5 ,  Patrick Hundsdoerfer  6 ,  Kirsten Minden  3  4  7 ,  Peter Krawitz  8
Affiliations
  • 1. Charité University Medicine Berlin, Pediatric Pneumology and Immunology, Augustenburger Platz 1, 13353, Berlin, Germany. [email protected].
  • 2. Center for Chronically Sick Children of the Charité, Augustenburger Platz 1, 13353, Berlin, Germany. [email protected].
  • 3. Charité University Medicine Berlin, Pediatric Pneumology and Immunology, Augustenburger Platz 1, 13353, Berlin, Germany.
  • 4. Center for Chronically Sick Children of the Charité, Augustenburger Platz 1, 13353, Berlin, Germany.
  • 5. Department of Pediatrics, University Clinic Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01037, Dresden, Germany.
  • 6. Charité University Medicine Berlin, Pediatric Oncology and Hematology, Augustenburger Platz 1, 13353, Berlin, Germany.
  • 7. Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin, Charitéplatz 1, 10117, Berlin, Germany.
  • 8. Charité University Medicine Berlin, Institute of Medical Genetics and Human Genetics, Augustenburger Platz 1, 13353, Berlin, Germany.
PMID: 27881174 DOI: 10.1186/s12969-016-0124-2
Abstract

Background: The pathophysiological origin of juvenile idiopathic Arthritis (JIA) is largely unknown. However, individuals with presumably pathogenic mutations in FAMIN have been reported, associating this gene with a rare subtype of this disorder. FAMIN, that is formerly also referred to as LACC1 or C13orf31, has recently been shown to play a crucial role in immune-metabolic functions and is involved in regulation of inflammasome activation and promotion of ROS production.

Case presentation: We describe two siblings with severe familial forms of juvenile Arthritis in which whole-exome-sequencing revealed a novel homozygous frameshift mutation (NM_153218.2:c.827delC¸. p.(T276fs*2) in FAMIN.

Conclusions: The observation of a new deleterious mutation adds further evidence that pathogenic mutations in FAMIN are causal for a monogenic form of JIA. Furthermore the associated phenotype is not restricted to systemic JIA, but can also be found in other forms of familial juvenile Arthritis.

Keywords
Exome sequencing, FAMIN, LACC1; Systemic juvenile idiopathic arthritis.