Finelli P, Pincelli A I, Russo S, Bonati M T, Recalcati M P, Masciadri M, Giardino D, Cavagnini F, Larizza L
Laboratory of Medical Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, Milan, Italy.
Clin Genet. 2007 Mar;71(3):195-204. doi: 10.1111/j.1399-0004.2007.00752.x.
FOG-2 (Friend of GATA 2) is a transcriptional cofactor able to differentially regulate the expression of GATA-target genes in different promoter contexts. Mouse models evidenced that FOG-2 plays a role in congenital heart disease and normal testis development. In human, while FOG-2 mutations have been identified in sporadic cases of tetralogy of Fallot, no mutations are described to be associated with impaired gonadal function. We here describe a young boy with a balanced t(8;10)(q23.1;q21.1) translocation who was born with congenital secundum-type atrial septal defect and gonadal dysgenesis. Fluorescence in situ hybridization mapped the chromosome 8 translocation breakpoint (bkp) to within the IVS4 of the FOG-2 gene, whereas the chromosome 10 bkp was found to lie in a desert gene region. Quantitative analysis of FOG-2 expression revealed the presence of a truncated transcript but there was no detectable change in the expression of the genes flanking the 10q bkp, thus making it possible to assign the observed clinical phenotype to altered FOG-2 expression. Genetic and clinical analyses provide insights into the signaling pathways by which FOG-2 affects not only cardiac development but also gonadal function and its preservation.
FOG-2（GATA 2之友）是一种转录辅因子，能够在不同的启动子环境中差异调节GATA靶基因的表达。小鼠模型证明FOG-2在先天性心脏病和正常睾丸发育中起作用。在人类中，虽然在法洛四联症的散发病例中已鉴定出FOG-2突变，但未发现与性腺功能受损相关的突变。我们在此描述一名患有平衡t(8;10)(q23.1;q21.1)易位的小男孩，他出生时患有先天性继发孔型房间隔缺损和性腺发育不全。荧光原位杂交将8号染色体易位断点（bkp）定位到FOG-2基因的IVS4内，而10号染色体bkp位于一个基因荒漠区域。对FOG-2表达的定量分析显示存在截短的转录本，但在10q bkp侧翼基因的表达中未检测到变化，因此有可能将观察到的临床表型归因于FOG-2表达的改变。遗传和临床分析为FOG-2不仅影响心脏发育，还影响性腺功能及其维持的信号通路提供了见解。
