No evidence of WT1 gene mutations in children with congenital diaphragmatic hernia.

Children with congenital diaphragmatic hernia are born with a defect of the diaphragm that usually leads to a herniation of abdominal organs up into the thoracic cavity on the same side. The condition is often fatal, usually because of concomitant lung hypoplasia. The cause of this condition is unknown. The majority of cases are sporadic, but familial aggregation has been observed, indicating a genetic background. The tumor suppressor gene WT1 is involved in normal early urogenital development, and it is expressed in the mesothelium in the early human fetus. Recently, knockout mice homozygous for WT1 gene mutations were constructed. The embryos died between days 13 and 15 of gestation. Besides serious urogenital and thoracic malformations, the mice had defects in the diaphragm that caused herniation of lung tissue into the abdomen. These findings prompted the authors to screen for WT1 gene mutations in 27 children who had congenital diaphragmatic hernia. Using exon-per-exon polymerase chain reaction (PCR) amplifications and denaturing gradient gel electrophoresis, no WT1 mutations were detected. Southern blot analysis did not show any large rearrangements in the WT1 gene. These results exclude WT1 gene mutations as a major etiological factor for the isolated diaphragmatic defect. However, it is possible that other genes in the WT1 pathway are involved in this defect.