The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis

被引：16

作者：

Gomes, Julia do Amaral ^{[1
,2
,3
,4
]}

Kowalski, Thayne Woycinck ^{[1
,2
,3
,4
]}

Fraga, Lucas Rosa ^{[2
,3
,5
,6
]}

Macedo, Gabriel S. ^{[4
]}

Vieira Sanseverino, Maria Teresa ^{[1
,2
,3
,5
]}

Schuler-Faccini, Lavinia ^{[1
,2
,3
,5
]}

Luiz Vianna, Fernanda Sales ^{[1
,2
,3
,4
,5
,7
]}

机构：

[1] Univ Fed Rio Grande do Sul, Programa Posgrad Genet & Biol Mol, Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Lab Genet Med & Evolucao, Porto Alegre, RS, Brazil

[3] Inst Nacl Genet Med Populat INAGEMP, Porto Alegre, RS, Brazil

[4] HCPA, Lab Med Genom, Porto Alegre, RS, Brazil

[5] HCPA, Serv Genet Med, Sistema Nacl Informac Agentes Teratogen SIAT, Porto Alegre, RS, Brazil

[6] Univ Fed Rio Grande do Sul, Inst Ciencias Basicas Saude, Dept Ciencias Morfol, Porto Alegre, RS, Brazil

[7] HCPA, Lab Pesquisa Bioet & Et Ciencia LAPEBEC, Porto Alegre, RS, Brazil

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

ROBERTS-SYNDROME; LIMB; EMBRYOPATHY; MUTATIONS; IDENTIFICATION; PHENOTYPE; VARIANTS; MEMBER;

D O I：

10.1038/s41598-019-47739-8

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide affects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Recently, SALL4 and TBX5 were demonstrated to be thalidomide targets. To understand if these genes act in the TE development, we sequenced them in 27 individuals with TE; we verified how thalidomide affect them in human pluripotent stem cells (hPSCs) through a differential gene expression (DGE) analysis from GSE63935; and we evaluated how these genes are functionally related through an interaction network analysis. We identified 8 variants in ESCO2, 15 in SALL4 and 15 in TBX5. We compared allelic frequencies with data from ExAC, 1000 Genomes and ABraOM databases; eight variants were significantly different (p < 0.05). Eleven variants in SALL4 and TBXS were previously associated with cardiac diseases or malformations; however, in TE sample there was no association. Variant effect prediction tools showed 97% of the variants with potential to influence in these genes regulation. DGE analysis showed a significant reduction of ESCO2 in hPSCs after thalidomide exposure.

引用

页数：11

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