{
  "abstract": "Objective To characterise the clinical, immunologic and molecular genetic features of monogenic lupus in a large, ethnically diverse paediatric cohort and to evaluate genotype-phenotype correlations.Methods We conducted a retrospective multicentre study of 100 children with genetically confirmed monogenic lupus diagnosed before the age of 14 years. Patients were enrolled between 2000 and 2025 from centres in Saudi Arabia, Iran, Russia, Italy, Palestine and Oman. Demographic data, clinical manifestations, immunological findings, genetic results, treatments and outcomes were systematically analysed. Multivariable logistic regression was used to evaluate associations between specific genotypes and clinical phenotypes.Results The median age at onset was 24 months, with 69% of patients carrying homozygous pathogenic mutations. The most frequently implicated genes were C1Q (26%) and DNASE1L3 (25%), representing complement and type I interferon pathways, respectively. Mucocutaneous (84%), musculoskeletal (74%) and neurological (42%) were the most common clinical features. Disease burden was substantial, reflected by a median Paediatric Systemic Disease Index score of 3 and a mortality rate of 16%. Distinct ethnic clustering of specific gene mutations was observed. Genotype-phenotype analysis revealed that C1Q pathway defects were significantly associated with neurologic involvement, recurrent infections and anti-Sjögren’s syndrome antibody A (SSA)/SSB positivity, defining a characteristic clinical profile. In contrast, DNASE1L3-related disease showed inverse associations with several clinical features, including recurrent infections, suggesting a different pathogenic and clinical trajectory.Conclusion This large international cohort highlights the clinical and genetic heterogeneity of monogenic lupus. C1Q and DNASE1L3 mutations account for most cases and display distinct phenotypic profiles. These findings underscore the need for genotype-guided diagnostic and therapeutic approaches in monogenic lupus.",
  "authors": [
    {
      "affiliations": [
        "Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia",
        "Alfaisal University College of Medicine, Riyadh, Saudi Arabia"
      ],
      "name": "Sulaiman M Al-Mayouf"
    },
    {
      "affiliations": [
        "Children’s Medical Center, Tehran, Iran (the Islamic Republic of)",
        "Department of Pediatrics, Tehran University of Medical Sciences, Tehran, Iran (the Islamic Republic of)"
      ],
      "name": "Vahid Ziaee"
    },
    {
      "affiliations": [
        "School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran (the Islamic Republic of)",
        "Golestan Rheumatology Research Center, Golestan University of Medical Sciences, Gorgan, Iran (the Islamic Republic of)"
      ],
      "name": "Nasim Movahedi"
    },
    {
      "affiliations": [
        "Saint Petersburg State Pediatric Medical University, Sankt Peterburg, Russian Federation"
      ],
      "name": "Mikhail Kostik"
    },
    {
      "affiliations": [
        "Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia"
      ],
      "name": "Raghad Alhuthil"
    },
    {
      "affiliations": [
        "Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia"
      ],
      "name": "Abdullah Alsonbul"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Prince Sultan Medical Military City, Riyadh, Saudi Arabia"
      ],
      "name": "Abdulrahman Asiri"
    },
    {
      "affiliations": [
        "UOC Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto Giannina Gaslini, Genoa, Italy",
        "DINOGMI, University of Genoa, Genoa, Italy"
      ],
      "name": "Stefano Volpi"
    },
    {
      "affiliations": [
        "UOC Reumatologia e Malattie Autoinfiammatorie, IRCCS Istituto Giannina Gaslini, Genoa, Italy"
      ],
      "name": "Marco Gattorno"
    },
    {
      "affiliations": [
        "King Fahad Armed Forces Hospital, Jeddah, Saudi Arabia"
      ],
      "name": "Mahmoud Majeed"
    },
    {
      "affiliations": [
        "Department of Child Health, Royal Hospital, Muscat, Oman"
      ],
      "name": "Safiya Al Abrawi"
    },
    {
      "affiliations": [
        "King Fahad Hospital, Jazan, Saudi Arabia"
      ],
      "name": "Mada Yateem"
    },
    {
      "affiliations": [
        "Security Forces Hospital in Riyadh, Riyadh, Saudi Arabia"
      ],
      "name": "Ashwag Alharthi"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Al-Quds University, Abu Dis, Palestine, State of"
      ],
      "name": "Sima Al-Saoud"
    },
    {
      "affiliations": [
        "Department of Translational Genomics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia"
      ],
      "name": "Anas M Alazami"
    },
    {
      "affiliations": [
        "Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia"
      ],
      "name": "Alhanouf AlSaleem"
    }
  ],
  "title": "Genetic and phenotypic landscape of monogenic lupus: insights from an international cohort",
  "uid": "3a3016a6-c06f-5c1c-b982-b7162dcb8130"
}