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Sequence analysis in Familial Mediterranean Fever patients with no confirmatory genotype

  • Genes and Disease
  • Published:
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Abstract

Introduction/objectives

Familial Mediterranean Fever (FMF) is a genetic disorder of the innate immunity characterized by chronic inflammatory state. The diagnosis is mainly based on clinical criteria and supported by genotyping, especially in atypical phenotypes. The primary objective was to depict the Familial Mediterranean Fever (FMF) genotype of Greek patients and investigate the contribution of Next Generation Sequencing (NGS) beyond the contemporary techniques [(Polymerase Chain Reaction (PCR)/hybridization and Non-Isotopic RNase Cleavage Assay (NIRCA). The secondary objective was to unravel any associations between the mutated genes with the disease course and response to treatment.

Methods

In this single center, retrospective study 31 patients with clinical diagnosis with FMF, but non-conclusive genetic analysis with PCR/hybridization and NIRCA, underwent NGS genotyping.

Results

PCR/NIRCA detected ≥ 1 mutation in 25/31 patients, most frequently M694V (29%), while NGS in 26/31 (83.9%), most frequently R202Q (61.3%). NGS genetically confirmed the clinical diagnosis (heterozygosity to compound or complex genotype) in 19 (61.3%) patients of our cohort. R202Q was significantly more prevalent by NGS than by contemporary techniques (61.3 vs 12.9%, p = 0.0002) and was associated with FMF. Rare mutations were detected by NGS in 19.2% patients.

Conclusion

NGS clarifies the genetic profile of patients with atypical phenotypes and supports therapeutic management decisions. NGS unveiled the frequent involvement of R202Q in the pathogenesis of our FMF patients.

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Data availability

All data relevant to the study are included in the article. Additional information will be provided upon request.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. 1st Department of Paediatrics, Paediatric Immunology and Rheumatology Referral Center, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Vasiliki Sgouropoulou, Evangelia Farmaki, Vasiliki Tzimouli, Jenny Pratsidou-Gertsi & Maria Trachana

  2. Karyo Centre, Laboratory of Molecular Biology and Genetics, Karyo Center, Thessaloniki, Greece

    Theophanis Papadopoulos

  3. Konstantinoupoleos 49, Thessaloniki, 54642, Greece

    Vasiliki Sgouropoulou

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  1. Vasiliki Sgouropoulou
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by VS, MT and EF. The first draft of the manuscript was written by VS and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Vasiliki Sgouropoulou.

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The institutional bioethics committee of Aristotle University of Thessaloniki has approved the research protocol. The study complies with the 1964 Declaration of Helsinki and its later amendments.

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Informed consent to participate in the study has been obtained from the parents and/or the participants themselves when aged over 16 years.

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Sgouropoulou, V., Farmaki, E., Papadopoulos, T. et al. Sequence analysis in Familial Mediterranean Fever patients with no confirmatory genotype. Rheumatol Int 42, 15–22 (2022). https://doi.org/10.1007/s00296-021-04913-4

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  • DOI: https://doi.org/10.1007/s00296-021-04913-4

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