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

Nature Genetics volume 43, pages 1186–1188 (2011)Cite this article

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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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Figure 1: Identification of a new inactivating mutation in DNASE1L3 in a Mendelian phenocopy of SLE.

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Acknowledgements

We would like to thank the families for their participation and the Genotyping and Sequencing Core Facilities at King Faisal Specialist Hospital and Research Center for their technical help. This work is supported by a Dubai Harvard Foundation for Medical Research collaborative grant (FSA).

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Author notes

  1. Sulaiman M Al-Mayouf, Asma Sunker and Reem Abdwani: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Pediatrics, Rheumatology Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Sulaiman M Al-Mayouf & Abdullah Al Sonbul

  2. Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

    Asma Sunker, Mais Hashem, Hanif Khalak, Latifa Al-Jebali & Fowzan S Alkuraya

  3. Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman

    Reem Abdwani & Eiman Abdallah

  4. Department of Child Health, Royal Hospital, Muscat, Oman

    Safiya Al Abrawi & Nadia Alhashmi

  5. Department of Genetics, Sultan Qaboos University Hospital, Muscat, Oman

    Fathiya Almurshedi

  6. Division of Rheumatology, Department of Medicine, King Fahad National Guard Hospital and King Abdullah International Medical Research Center, Riyadh, Saudi Arabia

    Wafaa Sewairi & Saleh Al Motywee

  7. Department of Medical Genetics, King Faisal Specialist Hospital, Riyadh, Saudi Arabia

    Aliya Qari & Mohammed Al-Owain

  8. Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia

    Mohammed Al-Owain & Fowzan S Alkuraya

  9. Department of Medicine, Riyadh Military Hospital, Riyadh, Saudi Arabia

    Hanan Al-Rayes

  10. Department of Pediatrics, King Khalid University Hospital and College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Fowzan S Alkuraya

Authors
  1. Sulaiman M Al-Mayouf
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  2. Asma Sunker
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  14. Mais Hashem
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  15. Hanif Khalak
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  16. Latifa Al-Jebali
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  17. Fowzan S Alkuraya
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Contributions

The study was conceived of by S.M.A.-M., F.A., M.A.-O., L.A.-J. and F.S.A. Data were collected by S.M.A.-M., A.S., R.A., S.A.A., F.A., N.A., A.A.-S., W.S., A.Q., E.A., M.A.-O., S.A.M., H.A.-R., M.H., L.A.-J. and F.S.A. Data analysis was performed by A.S., R.A., H.K., L.A.-J. and F.S.A. The manuscript was written by F.S.A. and edited by S.M.A.-M., A.S., R.A., S.A.A., F.A., N.A. and L.A.-J.

Corresponding author

Correspondence to Fowzan S Alkuraya.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Methods, Supplementary Figures 1–3 and Supplementary Table 1 (PDF 917 kb)

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Al-Mayouf, S., Sunker, A., Abdwani, R. et al. Loss-of-function variant in DNASE1L3 causes a familial form of systemic lupus erythematosus. Nat Genet 43, 1186–1188 (2011). https://doi.org/10.1038/ng.975

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  • DOI: https://doi.org/10.1038/ng.975

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