Mitochondrial cardiomyopathy and ventricular arrhythmias associated with biallelic variants in C1QBP

Gregory Webster*, Meredith Reynolds, Nicoleta C. Arva, Lisa M. Dellefave-Castillo, Hilary S. McElligott, Amber Kofman, Aleksandra Laboski, Defne Magnetta, Alfred L. George, Elizabeth M. McNally, Megan J. Puckelwartz

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Patients with biallelic mutations in the nuclear-encoded mitochondrial gene C1QBP/p32 have been described with syndromic features and autosomal recessive cardiomyopathy. We describe the clinical course in two siblings who developed cardiomyopathy and ventricular fibrillation in infancy. We provide genomic analysis and clinical-pathologic correlation. Both siblings had profound cardiac failure with ventricular arrhythmia. One child died suddenly. The second sibling survived resuscitation but required extracorporeal cardiopulmonary support and died shortly afterward. On cardiac autopsy, the left ventricle was hypertrophied in both children. Histological examination revealed prominent cardiomyocyte cytoplasmic clearing, and electron microscopy confirmed abnormal mitochondrial structure within cardiomyocytes. DNA sequencing revealed compound heterozygous variants in C1QBP (p.Thr40Asnfs*45 and p.Phe204Leu) in both children. Family segregation analysis demonstrated each variant was inherited from an unaffected, heterozygous parent. Inherited loss of C1QBP/p32 is associated with recessive cardiomyopathy, ventricular fibrillation, and sudden death in early life. Ultrastructural mitochondrial evaluation in the second child was similar to findings in engineered C1qbp-deficient mice. Rapid trio analysis can define rare biallelic variants in genes that may be implicated in sudden death and facilitate medical management and family planning. (184/200).

Original languageEnglish (US)
Pages (from-to)2496-2501
Number of pages6
JournalAmerican Journal of Medical Genetics, Part A
Issue number8
StatePublished - Aug 2021


  • C1QBP
  • mitochondrial cardiomyopathy
  • p32
  • pediatrics
  • sudden death
  • ventricular fibrillation

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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