Skip to main content

BRIEF RESEARCH REPORT article

Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 15 - 2024 | doi: 10.3389/fgene.2024.1493295

Genewise detection of variants in MEFV gene using nanopore sequencing

Provisionally accepted
Lilit Ghukasyan Lilit Ghukasyan 1Gisane Khachatryan Gisane Khachatryan 1,2Tamara Sirunyan Tamara Sirunyan 1,2Arpine Minasyan Arpine Minasyan 1Siras Hakobyan Siras Hakobyan 1,3Andranik Chavushyan Andranik Chavushyan 1Vadruhi Hayrapetyan Vadruhi Hayrapetyan 2Hovsep Ghazaryan Hovsep Ghazaryan 1Gevorg Martirosyan Gevorg Martirosyan 1Mkrtchyan Gohar Mkrtchyan Gohar 1Valentina Vardanyan Valentina Vardanyan 4,5Vahan Mukuchyan Vahan Mukuchyan 6Roksana Zakharyan Roksana Zakharyan 1,2*Arsen Arakelyan Arsen Arakelyan 1,2*
  • 1 Institute of Molecular Biology, Armenian National Academy of Sciences, Yerevan, Armenia
  • 2 Russian-Armenian (Slavonic) University, Yerevan, Yerevan, Armenia
  • 3 Armenian Bioinformatics Institute (ABI), Yerevan, Armenia
  • 4 Department of Rheumatology, Yerevan State Medical University after Mkhitar Heratsi (YSMU), Yerevan, Armenia
  • 5 Department of Rheumatology, “Mikaelyan” Institute of Surgery, Yerevan, Armenia
  • 6 Nairi Medical Center, Yerevan, Armenia

The final, formatted version of the article will be published soon.

    Familial Mediterranean Fever (FMF) is a genetic disorder with complex inheritance patterns and genotype-phenotype associations, and it is highly prevalent in Armenia. FMF typically follows an autosomal recessive inheritance pattern (OMIM: 249100), though it can occasionally display a rare dominant inheritance pattern with variable penetrance (OMIM։134610). The disease is caused by mutations in the MEFV gene, which encodes the pyrin protein. While the 26 most prevalent mutations account for nearly 99% of all FMF cases, more than 60 pathogenic mutations have been identified. In this study, we aimed to develop an affordable nanopore sequencing method for fulllength MEFV gene mutation detection to aid in the diagnosis and screening of FMF. PAGE \* Arabic \* MERGEFORMAT We employed a multiplex amplicon sequencing approach, allowing for the processing of up to 12 samples on both Flow cells and Flongle flow cells. The results demonstrated near-complete concordance between nanopore variant calling and qPCR genotypes. Moreover, nanopore sequencing identified additional variants, which were confirmed by whole exome sequencing. Additionally, intronic and UTR variants were detected.Our findings demonstrate the feasibility of full-gene nanopore sequencing for detecting FMFassociated pathogenic variants. The method is cost-effective, with costs comparable to those of the qPCR test, making it particularly suitable for settings with limited laboratory infrastructure. Further clinical validation using larger sample cohorts will be necessary.

    Keywords: Familial Mediterranean Fever, FMF, MEFV, nanopore sequencing, Variant detection, Genetic Testing

    Received: 08 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Ghukasyan, Khachatryan, Sirunyan, Minasyan, Hakobyan, Chavushyan, Hayrapetyan, Ghazaryan, Martirosyan, Gohar, Vardanyan, Mukuchyan, Zakharyan and Arakelyan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Roksana Zakharyan, Russian-Armenian (Slavonic) University, Yerevan, 0051, Yerevan, Armenia
    Arsen Arakelyan, Institute of Molecular Biology, Armenian National Academy of Sciences, Yerevan, 0014, Armenia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.