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

被引：349

作者：

Al-Mayouf, Sulaiman M. ^{[2
]}

Sunker, Asma ^{[1
]}

Abdwani, Reem ^{[3
]}

Al Abrawi, Safiya ^{[4
]}

Almurshedi, Fathiya ^{[5
]}

Alhashmi, Nadia ^{[4
]}

Al Sonbul, Abdullah ^{[2
]}

Sewairi, Wafaa ^{[6
,7
]}

Qari, Aliya ^{[8
]}

Abdallah, Eiman ^{[3
]}

Al-Owain, Mohammed ^{[8
,9
]}

Al Motywee, Saleh ^{[6
,7
]}

Al-Rayes, Hanan ^{[10
]}

Hashem, Mais ^{[1
]}

Khalak, Hanif ^{[1
]}

Al-Jebali, Latifa ^{[1
]}

Alkuraya, Fowzan S. ^{[1
,9
,11
,12
]}

机构：

[1] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia

[2] King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Rheumatol Sect, Riyadh 11211, Saudi Arabia

[3] Sultan Qaboos Univ Hosp, Dept Child Hlth, Muscat, Oman

[4] Royal Hosp, Dept Child Hlth, Muscat, Oman

[5] Sultan Qaboos Univ Hosp, Dept Genet, Muscat, Oman

[6] King Fahad Natl Guard Hosp, Div Rheumatol, Dept Med, Riyadh, Saudi Arabia

[7] King Abdullah Int Med Res Ctr, Riyadh, Saudi Arabia

[8] King Faisal Specialist Hosp & Res Ctr, Dept Med Genet, Riyadh, Saudi Arabia

[9] Alfaisal Univ, Coll Med, Dept Anat & Cell Biol, Riyadh, Saudi Arabia

[10] Riyadh Mil Hosp, Dept Med, Riyadh, Saudi Arabia

[11] King Saud Univ, Coll Med, Riyadh 11461, Saudi Arabia

[12] King Khalid Univ Hosp, Dept Pediat, Riyadh 11472, Saudi Arabia

来源：

NATURE GENETICS | 2011年 / 43卷 / 12期

关键词：

SUSCEPTIBILITY VARIANTS; DEOXYRIBONUCLEASE I; PXK;

D O I：

10.1038/ng.975

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1186 / 1188

页数：3

共 13 条

[1] Autozygome decoded
Alkuraya, Fowzan S.
[J]. GENETICS IN MEDICINE, 2010, 12 (12) : 765 - 771
[2] ALMAYOUF S, RHEUMATOL I IN PRESS
[3] Biological functions of the disulfides in bovine pancreatic deoxyribonuclease
Chen, WJ
Lee, IS
Chen, CY
Liao, TH
[J]. PROTEIN SCIENCE, 2004, 13 (04) : 875 - 883
[4] Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci
Harley, John B.
Alarcon-Riquelme, Marta E.
Criswell, Lindsey A.
Jacob, Chaim O.
Kimberly, Robert P.
Moser, Kathy L.
Tsao, Betty P.
Vyse, Timothy J.
Langefeld, Carl D.
[J]. NATURE GENETICS, 2008, 40 (02) : 204 - 210
[5] KIM EM, RHEUMATOL I IN PRESS
[6] Features of systemic lupus erythematosus in Dnase1-deficient mice
Napirei, M
Karsunky, H
Zevnik, B
Stephan, H
Mannherz, HG
Möröy, T
[J]. NATURE GENETICS, 2000, 25 (02) : 177 - 181
[7] Identification, localization, and expression of two novel human genes similar to deoxyribonuclease I
Rodriguez, AM
Rodin, D
Nomura, H
Morton, CC
Weremowicz, S
Schneider, MC
[J]. GENOMICS, 1997, 42 (03) : 507 - 513
[8] ENDOGENOUS CIRCULATING DNA IN SYSTEMIC LUPUS-ERYTHEMATOSUS - OCCURRENCE AS MULTIMERIC COMPLEXES BOUND TO HISTONE
RUMORE, PM
STEINMAN, CR
[J]. JOURNAL OF CLINICAL INVESTIGATION, 1990, 86 (01) : 69 - 74
[9] Evaluating the Heritability Explained by Known Susceptibility Variants: A Survey of Ten Complex Diseases
So, Hon-Cheong
Gui, Allen H. S.
Cherny, Stacey S.
Sham, Pak C.
[J]. GENETIC EPIDEMIOLOGY, 2011, 35 (05) : 310 - 317
[10] Caucasian-specific allele in non-synonymous single nucleotide polymorphisms of the gene encoding deoxyribonuclease I-like 3, potentially relevant to autoimmunity, produces an inactive enzyme
Ueki, Misuzu
Takeshita, Haruo
Fujihara, Junko
Iida, Reiko
Yuasa, Isao
Kato, Hideaki
Panduro, Arturo
Nakajima, Tamiko
Kominato, Yoshihiko
Yasuda, Toshihiro
[J]. CLINICA CHIMICA ACTA, 2009, 407 (1-2) : 20 - 24

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