TY - JOUR
T1 - Biallelic variants in ETV2 in a family with congenital heart defects, vertebral abnormalities and preaxial polydactyly
AU - Basel-Salmon, Lina
AU - Ruhrman-Shahar, Noa
AU - Barel, Ortal
AU - Hagari, Ofir
AU - Marek-Yagel, Dina
AU - Azulai, Noy
AU - Bazak, Lily
AU - Svirsky, Ran
AU - Reznik-wolf, Haike
AU - Lidzbarsky, Gabriel Arie
AU - Shohat, Mordechai
N1 - Publisher Copyright:
© 2020 Elsevier Masson SAS
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
KW - Autosomal recessive
KW - Congenital heart defect
KW - Exome sequencing
KW - Polydactyly
KW - Vertebral abnormalities
UR - http://www.scopus.com/inward/record.url?scp=85099264318&partnerID=8YFLogxK
U2 - 10.1016/j.ejmg.2020.104124
DO - 10.1016/j.ejmg.2020.104124
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C2 - 33359164
AN - SCOPUS:85099264318
SN - 1769-7212
VL - 64
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 2
M1 - 104124
ER -