Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease that causes substantial morbidity. As is typical for many other multifactorial disorders, much of the heritability of SLE remains unknown. We identified a rare autosomal recessive form of SLE, in which autozygome analysis revealed a null mutation in the DNASE1L3 gene. The DNASE1L3-related SLE we describe was always pediatric in onset and correlated with a high frequency of lupus nephritis. Our findings confirm the critical role of impaired clearance of degraded DNA in SLE pathogenesis.
Rheumatology Section, Department of Pediatrics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
Sulaiman M
SM
Al-Mayouf
Asma
A
Sunker
Reem
R
Abdwani
Safiya Al
SA
Abrawi
Fathiya
F
Almurshedi
Nadia
N
Alhashmi
Abdullah
A
Al Sonbul
Wafaa
W
Sewairi
Aliya
A
Qari
Eiman
E
Abdallah
Mohammed
M
Al-Owain
Saleh
S
Al Motywee
Hanan
H
Al-Rayes
Mais
M
Hashem
Hanif
H
Khalak
Latifa
L
Al-Jebali
Fowzan S
FS
Alkuraya
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003241:Consanguinity; D004706:Endodeoxyribonucleases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D040941:Heredity; D006720:Homozygote; D006801:Humans; D008126:Lod Score; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008297:Male; D017384:Sequence Deletion; D055815:Young Adult
C485421:DNASE1L3 protein, human; D004706:Endodeoxyribonucleases