PT  - JOURNAL ARTICLE
AU  - Ezgi Deniz Batu
AU  - Can Koşukcu
AU  - Ekim Taşkıran
AU  - Sezgin Sahin
AU  - Sema Akman
AU  - Betül Sözeri
AU  - Erbil Ünsal
AU  - Yelda Bilginer
AU  - Ozgur Kasapcopur
AU  - Mehmet Alikaşifoğlu
AU  - Seza Ozen
TI  - Whole Exome Sequencing in Early-onset Systemic Lupus Erythematosus
AID  - 10.3899/jrheum.171358
DP  - 2018 Dec 01
TA  - The Journal of Rheumatology
PG  - 1671--1679
VI  - 45
IP  - 12
4099  - http://www.jrheum.org/content/45/12/1671.short
4100  - http://www.jrheum.org/content/45/12/1671.full
SO  - J Rheumatol2018 Dec 01; 45
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.