Are CUL3 variants an underreported cause of congenital heart disease?

Daniela Di Francesco; Anne Swenerton; Wenhui Laura Li; Christopher Dunham; Glenda Hendson; Cornelius F Boerkoel

doi:10.1002/ajmg.a.63387

Are CUL3 variants an underreported cause of congenital heart disease?

Am J Med Genet A. 2023 Dec;191(12):2903-2907. doi: 10.1002/ajmg.a.63387. Epub 2023 Sep 4.

Authors

Daniela Di Francesco¹, Anne Swenerton^{2

3}, Wenhui Laura Li⁴, Christopher Dunham⁵, Glenda Hendson⁵, Cornelius F Boerkoel^{2

3}

Affiliations

¹ MD Undergraduate Program, University of British Columbia, Vancouver, British Columbia, Canada.
² Provincial Medical Genetics Program, B.C. Women's Hospital, Vancouver, British Columbia, Canada.
³ Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
⁴ Breakthrough Genomics, Irvine, California, USA.
⁵ Department of Pathology and Laboratory Medicine, University of British Columbia and BC Children's Hospital, Vancouver, British Columbia, Canada.

PMID: 37665043
DOI: 10.1002/ajmg.a.63387

Abstract

Complex heart defects (CHD) are a common malformation associated with disruption of developmental pathways. The Cullin-RING ligases (CRLs) are multi-subunit E3 ubiquitin ligases in which Cullin 3 (CUL3) serves as a scaffolding subunit. Heterozygous CUL3 variants have been associated with neurodevelopmental disorders and pseudohypoaldosteronism type IIE. We report a fetus with CHD and a de novo CUL3 variant (NM_003590.4:c.[1549_1552del];[=], p.(Ser517Profs*23)) and review CUL3 variants reported with CHD. We postulate that CUL3 variants predispose to CHD and hypothesize mechanisms of pathogenesis.

Keywords: CUL3; congenital heart disease.

Publication types

Case Reports

MeSH terms

Cullin Proteins* / genetics
Cullin Proteins* / metabolism
Heart Defects, Congenital* / genetics
Humans
Ubiquitin-Protein Ligases

Substances

Cullin Proteins
Ubiquitin-Protein Ligases
CUL3 protein, human