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

https://doi.org/10.1016/S0022-3468(96)90412-1Get rights and content

Abstract

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 back-ground. 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 con-structed. 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.

References (23)

  • JP Crane

    Familial congenital diaphragmatic hernia: Prenatal diagnostic approach and analysis of twelve families

    Clin Genet

    (1979)
  • Cited by (17)

    • Abnormal lung development in congenital diaphragmatic hernia

      2017, Seminars in Pediatric Surgery
      Citation Excerpt :

      Deletion of part of chromosome 15 (15q26), which contains COUP-TFII, could account for some instances of CDH, although it is very rare (1.5%).85 Evidence for WT1 mutations is not encouraging in isolated CDH,86 but mutations exist when CDH occurs with Denys–Drash syndrome.87 CDH has been reported in Wilms׳ tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome, which involves WT1 deletion.88

    • Current concepts on the pathogenesis and etiology of congenital diaphragmatic hernia

      2013, Respiratory Physiology and Neurobiology
      Citation Excerpt :

      Further, there are reports linking defects in WT1 with CDH in humans (Devriendt et al., 1995; Reardon et al., 2004; Scott et al., 2005). However, it is clear that not all cases of CDH are associated with defects in WT1 (Nordenskjold et al., 1996). No mutations in COUP-TFII have yet been found in CDH samples (Scott, 2007; Goumy et al., 2010).

    • Congenital diaphragmatic hernia

      2002, Paediatric Respiratory Reviews
    View all citing articles on Scopus

    Supported by The Swedish Child Cancer Fund, the Crownprincess Lovisa Foundation, and the Samariten Foundation.

    View full text