Department of Cytogenetics, Laboratory Corporation of America/Dynacare, Seattle, WA 98122, USA.
Am J Med Genet A. 2013 Jul;161A(7):1755-8. doi: 10.1002/ajmg.a.35965. Epub 2013 May 21.
Microdeletions of 8p23.1 are mediated by low copy repeats and can cause congenital diaphragmatic hernia (CDH) and cardiac defects. Within this region, point mutations of the GATA4 gene have been shown to cause cardiac defects. However, the cause of CDH in these deletions has been difficult to determine due to the paucity of mutations that result in CDH, the lack of smaller deletions to refine the region and the reduced penetrance of CDH in these large deletions. Mice deficient for one copy of the Gata4 gene have been described with CDH and heart defects suggesting mutations in Gata4 can cause the phenotype in mice. We report on the SNP microarray analysis on two fetuses with deletions of 8p23.1. The first had CDH and a ventricular septal defect (VSD) on ultrasonography and a family history of a maternal VSD. Microarray analysis detected a 127-kb deletion which included the GATA4 and NEIL2 genes which was inherited from the mother. The second fetus had an incomplete atrioventricular canal defect on ultrasonography. Microarray analysis showed a 315-kb deletion that included seven genes, GATA4, NEIL2, FDFT1, CTSB, DEFB136, DEFB135, and DEFB134. These results suggest that haploinsufficiency of the two genes in common within 8p23.1; GATA4 and NEIL2 can cause CDH and cardiac defects in humans.
8p23.1 微缺失是由低拷贝重复序列介导的，可导致先天性膈疝 (CDH) 和心脏缺陷。在该区域，已经表明 GATA4 基因突变会导致心脏缺陷。然而，由于导致 CDH 的突变很少，较小的缺失不足以精确定位该区域，并且这些大缺失的 CDH 外显率降低，因此这些缺失导致 CDH 的原因一直难以确定。已经描述了 Gata4 基因的一个拷贝缺失的小鼠存在 CDH 和心脏缺陷，这表明 Gata4 中的突变可以在小鼠中引起表型。我们报告了两个 8p23.1 缺失胎儿的 SNP 微阵列分析结果。第一个胎儿在超声检查中存在 CDH 和室间隔缺损 (VSD)，且有母亲 VSD 的家族史。微阵列分析检测到一个 127-kb 的缺失，其中包括 GATA4 和 NEIL2 基因，这些基因是从母亲那里遗传来的。第二个胎儿在超声检查中存在不完全性房室管缺损。微阵列分析显示一个 315-kb 的缺失，其中包括七个基因，即 GATA4、NEIL2、FDFT1、CTSB、DEFB136、DEFB135 和 DEFB134。这些结果表明，8p23.1 中两个常见基因（GATA4 和 NEIL2）的单倍体不足可导致人类 CDH 和心脏缺陷。
