A homozygous loss-of-function C1S mutation is associated with Kikuchi-Fujimoto disease

Abstract

Background: Kikuchi-Fujimoto disease (KFD) is a self-limited inflammatory disease of unknown pathogenesis. Familial cases have been described and defects in classical complement components C1q and C4 have been identified in some patients. Material and methods: We describe genetic and immune investigations of a 16 years old Omani male, a product of consanguineous marriage, who presented with typical clinical and histological features of KFD. Results: We identified a novel homozygous single base deletion in C1S (c.330del; p. Phe110LeufsTer23) resulting in a defect in the classical complement pathway. The patient was negative for all serological markers of SLE. In contrast, two female siblings (also homozygous for the C1S mutation), one has autoimmune thyroid disease (Hashimoto thyroiditis) and a positive ANA and the other sibling has serology consistent with SLE. Conclusion: We report the first association between C1s deficiency and KFD.