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Rare Structural Variants Uncovered by Optical Genome Mapping in Multisystem Inflammatory Syndrome in Children (MIS-C)

Catherine A Brownstein1,2, Caspar I van der Made3, Kristin Cabral1

  • 1Division of Genetics and Genomics The Manton Center For Orphan Disease Research Harvard Medical School Boston Children's Hospital Boston Massachusetts USA.

Advanced Genetics (Hoboken, N.J.)
|December 31, 2025
PubMed

Insights

Optical Genome Mapping identified rare structural variants in children with Multisystem Inflammatory Syndrome (MIS-C). These genetic findings may explain disease variations and susceptibility to severe COVID-19 or Kawasaki Disease.

Area of Science:

  • Genetics
  • Pediatrics
  • Immunology

Background:

  • Multisystem Inflammatory Syndrome in Children (MIS-C) is a serious pediatric condition linked to SARS-CoV-2 infection.
  • MIS-C often involves multiorgan inflammation and cardiovascular issues.
  • Understanding the genetic underpinnings of MIS-C is crucial for explaining disease heterogeneity.

Purpose of the Study:

  • To investigate the utility of Optical Genome Mapping (OGM) in identifying structural variants in patients with MIS-C.
  • To explore potential genetic factors contributing to MIS-C, MIS-C-like presentations, and severe COVID-19 outcomes.

Main Methods:

  • A prospective cohort study involving 14 pediatric patients (11 with MIS-C, 3 with MIS-C-like presentations).
  • Optical Genome Mapping (OGM) was performed on all patients.
  • Structural Variants (SVs) and Copy Number Variations (CNVs) were identified and filtered against control databases.

Main Results:

  • Seven out of 14 patients (50%) had prioritized variants near genes involved in immune regulation or SARS-CoV-2 response.
  • Identified variants included insertions/deletions in ORAI1, STAT4, ITPR1, BATF, CFHR5, and DOCK2.
  • OGM revealed SVs potentially influencing inflammation, COVID-19 severity, and Kawasaki Disease susceptibility.

Conclusions:

  • OGM is a feasible and valuable tool for assessing complex pediatric syndromes like MIS-C.
  • Rare structural variants may contribute to the diverse clinical presentations and severity of MIS-C.
  • These findings offer biologically plausible mechanisms for MIS-C heterogeneity and susceptibility.

Keywords:
MIS‐CSARS‐CoV‐2optical genome mapping

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