Biallelic variants in ETV2 in a family with congenital heart defects, vertebral abnormalities and preaxial polydactyly

Lina Basel-Salmon, Noa Ruhrman-Shahar, Ortal Barel, Ofir Hagari, Dina Marek-Yagel, Noy Azulai, Lily Bazak, Ran Svirsky, Haike Reznik-wolf, Gabriel Arie Lidzbarsky, Mordechai Shohat

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4 Scopus citations


The combination of congenital heart defects and vertebral anomalies with or without additional abnormalities has been reported in many genetic disorders. We describe a family in which four consecutive pregnancies were characterized by the combination of fetal congenital heart malformations and vertebral anomalies. In addition, preaxial polydactyly was detected in one of the fetuses. Reanalysis of the non-diagnostic clinical exome data revealed compound heterozygous variants c.350del, p.(Gly117AlafsTer90) and c.757G > T, p.(Asp253Tyr) in ETV2 which have previously not been known to be associated with a phenotype in humans. In mice, Etv2 encodes an obligatory transcription factor involved in the generation of hematopoietic and endothelial cells. Its homozygous disruption results in embryonic lethality due to severe blood and vessel defects. The Etv2 promoter may be bound by Nkx2-5, a key transcription factor in heart development. Pathogenic variants in the NKx2-5 homolog in humans (NKX2-5) are related to congenital heart defects. The identification of additional fetuses or live-born individuals with biallelic pathogenic variants in ETV2 will shed further light on this presumably novel gene-phenotype association and on the full phenotypic spectrum.

Original languageEnglish
Article number104124
JournalEuropean Journal of Medical Genetics
Issue number2
StatePublished - Feb 2021
Externally publishedYes

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© 2020 Elsevier Masson SAS


  • Autosomal recessive
  • Congenital heart defect
  • Exome sequencing
  • Polydactyly
  • Vertebral abnormalities


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