TY - JOUR T1 - Genome-wide Sequencing in Rheumatic Diseases JF - The Journal of Rheumatology JO - J Rheumatol SP - 1614 LP - 1616 DO - 10.3899/jrheum.180951 VL - 45 IS - 12 AU - LINDA T. HIRAKI Y1 - 2018/12/01 UR - http://www.jrheum.org/content/45/12/1614.abstract N2 - As next-generation whole exome sequencing (WES) and whole genome sequencing (WGS) become increasingly available and affordable, their application has led to the growing identification of monogenic forms of rheumatic diseases, traditionally recognized as complex diseases. This is demonstrated in Batu, et al’s paper, “Whole Exome Sequencing in Early-onset Systemic Lupus Erythematosus,” appearing in this issue of The Journal1.The authors completed WES on 7 Turkish patients with systemic lupus erythematosus (SLE), with disease onset at 5 years of age or younger, from multiplex families (proband had an affected sibling) or who were offspring of consanguineous parents. They found 5 patients who were homozygous for variants predicted to alter the early complement cascade proteins. The sixth patient was homozygous for a 2-base pair deletion in DNASE1L3, a variant previously associated with young-onset SLE and hypocomplementemic urticarial vasculitis2,3,4. The seventh patient was homozygous for a number of variants, with an HDAC7 variant deemed a potentially causal variant.The Batu, et al paper1 highlights how the identification of causal genetic variants leading to monogenic lupus not only provides insights into the probable pathogenic variants responsible for disease and rare forms of monogenic lupus, but that these variants also implicate pathogenic mechanisms in SLE more broadly. One such example is DNASE1L3, an enzyme responsible for clearance of genetic material from apoptotic cellular debris. … Address correspondence to Dr. L.T. Hiraki. E-mail: linda.hiraki{at}sickkids.ca ER -