Biallelic variants in ETV2 in a family with congenital heart defects, vertebral abnormalities and preaxial polydactyly
Biallelic variants in ETV2 in a family with congenital heart defects, vertebral abnormalities and preaxial polydactyly
复制标题
DOI：
10.1016/j.ejmg.2020.104124
复制
发表时间：
2021-01-08
影响因子：
1.9
通讯作者：
Shohat, Mordechai
中科院分区：
文献类型：
--
作者：
Basel-Salmon, Lina;Ruhrman-Shahar, Noa;Shohat, Mordechai
先天性心脏缺陷和椎体异常合并或不合并其他异常在许多遗传疾病中都有报道。我们描述了一个家庭，其中四个连续怀孕的特点是合并胎儿先天性心脏畸形和椎体异常。此外，在其中一个胎儿中检测到前轴多指畸形。对非诊断性临床外显子组数据的重新分析显示，ETV2中存在复合杂合变异体c.350del, p.（Gly117AlafsTer90）和c.757G > T, p.(Asp253Tyr)，这些变异体以前未被发现与人类表型相关。在小鼠中，Etv2编码一种参与造血细胞和内皮细胞生成的强制性转录因子。它的纯合破坏导致胚胎致命，由于严重的血管缺陷。Etv2启动子可能与N10（2-5）结合，N10（2-5）是心脏发育的关键转录因子。人类NKx2-5同源基因的致病变异（NKx2-5）与先天性心脏缺陷有关。发现更多携带ETV2双等位致病变异的胎儿或活产个体，将进一步阐明这种可能的新型基因表型关联和完整的表型谱。
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 N10(2-5, 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 genephenotype association and on the full phenotypic spectrum.