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Paediatric systemic lupus erythematosus as a manifestation of constitutional mismatch repair deficiency
  1. Helen Toledano1,2,
  2. Naama Orenstein2,3,
  3. Efrat Sofrin3,
  4. Noa Ruhrman-Shahar4,
  5. Gil Amarilyo2,5,
  6. Lina Basel-Salmon2,4,
  7. Alan R Shuldiner6,
  8. Pola Smirin-Yosef7,
  9. Melyssa Aronson8,9,
  10. Hibs Al-tarrah8,
  11. Lili Bazak4,
  12. Claudia Gonzaga-Jauregui6,
  13. Uri Tabori8,10,
  14. Katharina Wimmer11,
  15. Yael Goldberg4
  1. 1 Department of Pediatric Hematology Oncology, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
  2. 2 Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
  3. 3 Pediatric Genetic Clinic, Schneider Children’s Medical Center of Israel, Petah Tikva, Israel
  4. 4 Recanati Genetics Institute, Rabin Medical Center, Petah Tikva, Israel
  5. 5 Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel
  6. 6 Regeneron Genetics Center, Tarrytown, New York, USA
  7. 7 Department of Molecular Biology, Genomic Bioinformatics Laboratory, Ariel University, Ariel, Israel
  8. 8 Zane Cohen Centre, Mount Sinai Hospital, Toronto, Ontario, Canada
  9. 9 Department of Haematology-Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada
  10. 10 The Arthur and Sonia Labbatt Brain Tumour Research Centre, The Hospital for Sick Children, Institute of Medical Sciences, The University of Toronto, Toronto, Ontario, Canada
  11. 11 Division of Human Genetics, Medical University Innsbruck, Innsbruck, Austria
  1. Correspondence to Dr Yael Goldberg, Recanati Genetics Institute, Rabin Medical Center, Petah Tikva 4941492, Israel; yaelgo43{at}


Biallelic mutations in any of the four mismatch repair genes MSH2, MSH6, MLH1 and PMS2 result in one of the most aggressive childhood cancer predisposition syndromes, termed constitutional mismatch repair deficiency (CMMRD) syndrome. In addition to a very high tumour risk, the CMMRD phenotype is often characterised by the presence of signs reminiscent of neurofibromatosis type 1. Although paediatric systemic lupus erythematosus (pSLE) has been reported so far in three patients with CMMRD, it has not been considered a diagnostic feature of the syndrome. We report here two additional female patients with pSLE and CMMRD due to biallelic pathogenic variants in MSH6. Hence, there are a total of five out of approximately 200 (2.5%) currently reported patients with CMMRD that also have pSLE, suggesting pSLE should raise the suspicion of a diagnosis of CMMRD, especially if supported by additional indicative features

  • Lynch
  • SLE
  • MSH6

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  • HT and NO contributed equally.

  • Contributors HT, NO, ES, GA, MA, H-AT and YG collected patients’ data and summarised clinical and genetic findings. NRS, LB-S, ARS, PS-Y, LB and CG-J participated in genetic studies, genetic analyses, bioinformatics and data interpretation. HT, GA, UT and YG followed and treated the patients. HT, UT, KW and YG drafted the manuscript. All coauthors critically reviewed the manuscript and approved the final submitted version.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests ARS and CG-J are full-time employees of the Regeneron Genetics Center from Regeneron Pharmaceuticals Inc. and receive stock options as part of compensation.

  • Patient consent for publication Parental/guardian consent obtained.

  • Provenance and peer review Not commissioned; externally peer reviewed.