Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus

SM Al-Mayouf, A Sunker, R Abdwani, SA Abrawi… - Nature …, 2011 - nature.com
SM Al-Mayouf, A Sunker, R Abdwani, SA Abrawi, F Almurshedi, N Alhashmi, A Al Sonbul…
Nature genetics, 2011nature.com
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 …
Abstract
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.
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