Utility of a targeted next-generation sequencing-based genetic screening panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome

Abstract

Objectives: This study aims to investigate a genetic panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome and examine its performance for an accurate differential diagnosis.

Patients and methods: Between January 2021 and January 2022, a total of 104 children with PFAPA syndrome (63 males, 41 females; mean age: 4.8±2.3 years; range, 1.2 to 8.9 years) were retrospectively analyzed. Next-generation sequencing test was performed using a custom QIAGEN- QIAseq™ Targeted DNA Panel which includes six genes namely ELANE, LPIN2, MEFV, MVK, NLRP3, and TNFRSF1A.

Results: Of 104 patients, 38 (36.5%) had variants in the genetic panel. The most common variants were found in the MEFV gene (n=35, 33.6%), the most frequent genotype was E148Q heterozygosity (n=16). Four and two patients were eventually diagnosed with Familial Mediterranean fever (FMF) and hyperimmunoglobulin D syndrome (HIDS), since they had confirmative biallelic pathogenic in the MEFV and MVK genes, respectively.

Conclusion: A genetic panel, including MEFV and MVK genes, may be useful in patients, clinically resembling PFAPA, since they may have HIDS or FMF, but lack typical features of the exact disease. Nonetheless, we believe that distinct genetic panels should be developed for different populations.

Citation: Kışla Ekinci RM, Anlaş Ö, Özalp Ö. Utility of a targeted next-generation sequencing-based genetic screening panel in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome. Arch Rheumatol 2023;38(2):299-306. doi: 10.46497/ArchRheumatol.2023.9681.

The study protocol was approved by the Adana City Training and Research Hospital Institutional Local Ethics Committee (date: 16.12.2021, no: 95/1678). The study was conducted in accordance with the principles of the Declaration of Helsinki.

A written informed consent was obtained from the parents and/or legal guardians of the patients.

Conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript: R.M.K.E.; Collected data and carried out the initial analyses: Ö.A.; Critically reviewed and revised the manuscript: Ö.Ö. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. All co-authors take full responsibility for the integrity of the study.

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

The authors received no financial support for the research and/or authorship of this article.

The data that support the findings of this study are available from the corresponding author upon reasonable request.