A prevalent MOCS2 variant in the Roma population is associated with a novel mild form of molybdenum cofactor deficiency
• A novel ultra-rare variant, rs776441627, located in two overlapping reading frames of the MOCS2, was identified in five Roma patients presenting a mild to asymptomatic clinical MoCD phenotype and a fully penetrant biochemical phenotype. • Functional studies of p.Ile82Phe (small MOCS2A subunit) and p.Leu19Phe (large MOCS2B subunit) demonstrate a strong reduction in molydopterin synthase complex formation and activity, consistent with the changes in biomarkers of MoCD observed in affected individuals. • The rs776441627 variant shows significantly elevated frequency among the Roma population, highlighting the importance of considering ethnic background in the differential diagnosis of MoCD. • Hypouricemia may provide an initial, generally available biochemical key marker indicator of molybdenum cofactor deficiency.
Authors
- Kateřina Pavelcová (ORCID: https://orcid.org/0000-0002-5379-7282)
- Michaela Křížková
- Cheryl Ann Winkler (ORCID: https://orcid.org/0000-0001-5552-0917)
- Blanka Stibůrková (ORCID: https://orcid.org/0000-0003-2465-1476)
- Jakub Krijt (ORCID: https://orcid.org/0000-0002-1738-654X)
- Tomáš Honzík (ORCID: https://orcid.org/0000-0003-4300-2519)
- Ivan Šebesta (ORCID: https://orcid.org/0000-0002-0917-7967)
- Sung Kweon Cho (ORCID: https://orcid.org/0000-0002-5929-7932)
- Juliane Roeper
- Viktor Kožich (ORCID: https://orcid.org/0000-0001-5820-5277)
- Jana Šaligová
- Jana Mašínová (ORCID: https://orcid.org/0000-0002-7446-1542)
- Velibor Tasić (ORCID: https://orcid.org/0000-0002-3377-1245)
- Günter Schwarz (ORCID: https://orcid.org/0000-0002-2118-9338)
Institutions
- University of Cologne (DE)
- Charles University (CZ)
- Institute of Rheumatology (CZ)
- Frederick National Laboratory for Cancer Research (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- Ajou University (KR)
- Ss. Cyril and Methodius University in Skopje (MK)
- Science Applications International Corporation (United States) (US)
Publication Details
- Journal
- European Journal of Pediatrics
- Published
- 2025-07-24
- DOI
- https://doi.org/10.1007/s00431-025-06335-x
- Citations
- 1
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.81
Funders
- Univerzita Karlova v Praze
- Univerzita Komenského v Bratislave
- Vanderbilt University Medical Center
- National Institutes of Health
- lékařská fakulta Univerzity Karlovy
- Instytut Biologii Medycznej Polskiej Akademii Nauk