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Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases

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Abstract

Introduction/objectives

The clinicians initially prefer to define patients with the systemic autoinflammatory disease (SAID)’s based on recommended clinical classification criteria; then, they confirm the diagnosis with genetic testing. We aimed to compare the initial phenotypic diagnoses of the patients who were followed up with the preliminary diagnosis of a monogenic SAID, and the genotypic results obtained from the next-generation sequence (NGS) panel.

Method

Seventy-one patients with the preliminary diagnosis of cryopyrin-associated periodic fever syndrome (CAPS), mevalonate kinase deficiency (MKD), or tumor necrosis factor-alpha receptor-associated periodic fever syndrome (TRAPS) were included in the study. The demographic data, clinical findings, laboratory results, and treatments were recorded. All patients were examined by NGS panel analysis including 16 genes. The genetic results were compared with the initial Federici score to determine whether they were compatible with each other.

Results

Thirty patients were initially classified as MKD, 22 as CAPS, and 19 as TRAPS. The frequency of clinical manifestations was urticarial rash 57.7%, diarrhea 49.2%, abdominal pain 47.8%, arthralgia 45%, oral aphthae 43.6%, myalgia 32.3%, tonsillitis 28.1%, and conjunctivitis 25.3%, respectively. After NGS gene panel screening, 13 patients were diagnosed with CAPS, 8 with MKD, 7 with familial Mediterranean fever, 5 with TRAPS, and 2 with NLRP12-associated periodic syndrome. The remaining 36 patients were genetically identified as undefined SAID since they were not classified as one of the defined SAIDs after the result of the NGS panel.

Conclusions

We have demonstrated that clinical diagnostic criteria may not always be sufficient to establish the correct diagnosis. There is still low accordance between clinical diagnoses and molecular analyses. In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should also be kept in mind in the differential diagnosis.

Key Points

• Monogenic autoinflammatory diseases can present with different clinical manifestations.

• The clinical diagnostic criteria may not always be sufficient to reach the correct diagnosis in autoinflammatory diseases.

• In the case of a patient with a preliminary diagnosis of a monogenic SAID with the negative result of target gene analysis, other autoinflammatory diseases should be kept in mind in the differential diagnosis.

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Acknowledgment

We are grateful to all participating children and their families.

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Authors and Affiliations

  1. Department of Pediatric Rheumatology, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey

    Betül Sözeri & Ferhat Demir

  2. Department of Pediatric Rheumatology, Kanuni Sultan Süleyman Training and Research Hospital, University of Health Sciences, Istanbul, Turkey

    Hafize Emine Sönmez, Şerife Gül Karadağ & Nuray Aktay Ayaz

  3. Department of Pediatric Genetics, Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey

    Yasemin Kendir Demirkol & Özlem Akgün Doğan

  4. Genomic Laboratory (GLAB), Umraniye Training and Research Hospital, University of Health Sciences, Istanbul, Turkey

    Hamdi Levent Doğanay

Authors
  1. Betül Sözeri
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  2. Ferhat Demir
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  3. Hafize Emine Sönmez
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  4. Şerife Gül Karadağ
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  5. Yasemin Kendir Demirkol
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  7. Hamdi Levent Doğanay
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  8. Nuray Aktay Ayaz
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Contributions

B.S. and F.D. developed the concept and designed the study; B.S., F.D., H.E.S., S.G.K., and N.A.A. performed research and acquired data; B.S., F.D., Ö.A.K., Y.K.D., and H.L.D. analyzed and interpreted data; B.S. and F.D. wrote and reviewed the manuscript. All authors reviewed and revised the final version of the manuscript and they take full responsibility for the integrity of the study.

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Correspondence to Ferhat Demir.

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Sözeri, B., Demir, F., Sönmez, H.E. et al. Comparison of the clinical diagnostic criteria and the results of the next-generation sequence gene panel in patients with monogenic systemic autoinflammatory diseases. Clin Rheumatol 40, 2327–2337 (2021). https://doi.org/10.1007/s10067-020-05492-8

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