Monogenic variants in Laccase domain-containing1 (LACC1) as the cause of juvenile arthritis

Abstract

Monogenic mutations in laccase domain-containing 1 (LACC1) are associated with clinical pictures that mimic severe courses of polyarticular or systemic juvenile idiopathic arthritis. The diseases are characterized by an early onset during the first year of life, afamilial clustering and ahigh inflammatory activity. The courses are mostly difficult to influence and often lead to sequelae. In this article four cases from two families are presented in which the homozygous mutation p.T276fs* in LACC1 was detected. The children initially suffered from polyarticular or systemic forms of juvenile arthritis. Of the patients two are currently being treated with tocilizumab and methotrexate and one female patient without a basis treatment is currently only receiving local repeated intra-articular steroids. A fourth female patient underwent an allogeneic bone marrow transplantation due to arelapse of an acute lymphatic leukemia. Since then, no further inflammatory symptoms have occurred. The cases presented are compared with the other 50courses published to date. In addition, recent studies investigating the influence of LACC1 mutations, particularly on macrophage function, are summarized.