RT Journal Article
SR Electronic
T1 Whole Exome Sequencing in Early-onset Systemic Lupus Erythematosus
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1671
OP 1679
DO 10.3899/jrheum.171358
VO 45
IS 12
A1 Ezgi Deniz Batu
A1 Can Koşukcu
A1 Ekim Taşkıran
A1 Sezgin Sahin
A1 Sema Akman
A1 Betül Sözeri
A1 Erbil Ünsal
A1 Yelda Bilginer
A1 Ozgur Kasapcopur
A1 Mehmet Alikaşifoğlu
A1 Seza Ozen
YR 2018
UL http://www.jrheum.org/content/45/12/1671.abstract
AB Objective. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder. Early-onset, familial, and/or syndromic SLE may reveal monogenic pathologies. The aim of this study was to examine genetic associations in patients with early-onset or familial SLE.Methods. We enrolled 7 SLE cases (from different families) with disease onset ≤ 5 years of age and family history consistent with an autosomal recessive inheritance. Whole exome sequencing (WES) was performed in 6 index cases. Suspected variants were confirmed by Sanger sequencing. We did not perform WES in 1 patient who had features similar to the first 3 cases; only the exons of C1QA, C1QB, and C1QC were screened with Sanger sequencing.Results. We demonstrated 2 novel and 3 previously reported variants in genes associated with SLE: a homozygous non-sense alteration (c.622C>T/p.Gln208Ter) in C1QA in 2 patients; homozygous non-sense alteration (c.79C>T/p.Gln27Ter) in C1QC in 1 (novel variant); homozygous missense alteration (c.100G>A/p.Gly34Arg) in C1QC in 1; homozygous missense alteration (c.1945G>C/p.Ala649Pro) in C1S in 1 (novel variant); and homozygous frameshift alteration (c.289_290delAC/p.Thr97Ilefs*2) in DNASE1L3 in 1 patient. Further, in 1 patient, we determined a strong candidate variant in HDAC7 (histone decetylase 7).Conclusion. Five patients had homozygous alterations in genes coding early complement proteins. This may lead to decreased clearance of apoptotic bodies. One patient had DNASE1L3 variant, which functions in the clearance of self-antigens. In 1 patient, we determined a novel gene that may be important in SLE pathogenesis. We suggest that monogenic causes/associations should be sought in early-onset and/or familial SLE.