Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019270 (hernia)
 15,856 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on a newborn infant with male pseudohermaphroditism and glomerular lesions (Denys-Drash syndrome) but without Wilms tumor. A constitutional heterozygous mutation in the WT1 gene (366Arg to His) was identified. In addition the child had a large diaphragmatic hernia, so far not described in Denys-Drash syndrome. The expression of the WT1 gene in pleural and abdominal mesothelium and the occurrence of diaphragmatic hernia in transgenic mice with a homozygous WT1 deletion strongly suggests that the diaphragmatic hernia in this patient is part of the malformation pattern caused by WT1 mutations.
 ...
PMID:Diaphragmatic hernia in Denys-Drash syndrome. 764 7

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.
 ...
PMID:No evidence of WT1 gene mutations in children with congenital diaphragmatic hernia. 881 58

Desmoplastic small round cell tumor is a rare, aggressive neoplasm that mainly affects young male patients and is characterized by a reciprocal translocation t(11;22)(p13;q12) associated with the EWS-WT1 gene fusion transcript. Clinical, histopathologic, immunohistochemical, and molecular genetics features were reviewed for 32 tumors. There were 29 male and three female patients, with ages from 6 to 54 years (mean, 25 years). The main clinical signs and symptoms included abdominal pain (eight patients), weight loss (five patients), and presence of umbilical hernia (four patients). Two tumors primarily involved the ethmoid sinus and the soft tissues of the scalp; the other tumors (mean size, 10 cm) involved the abdominal cavity (88%). One patient presented initially with an axillary lymph node metastasis. Generally, all tumors showed the typical histologic findings of variably sized clusters of small, round, or spindled cells lying in a desmoplastic stroma. The neoplastic cells in formalin-fixed, paraffin-embedded tissue sections were positive for desmin (dot pattern) (81% of the cases), WT1 (91%), keratin (87%), neuron-specific enolase (84%), CD99 (23%), and actin (3%). The EWS-WT1 gene fusion transcript was detected in 29 of 30 tumors. One tumor with typical clinicopathologic and immunohistochemical features did not show the gene fusion. Follow-up for 27 patients showed that 19 patients (70%) died of uncontrolled, local, or widespread metastatic disease 3-46 months (mean, 20 months) after diagnosis, and eight patients were alive with known evidence of disease. Occasionally, desmoplastic small round cell tumor lacks the classic clinical, histologic, and immunohistochemical features. This study emphasizes the utility of analysis of the EWS-WT1 gene fusion transcript, which was performed on paraffin-embedded tissues, to confirm the diagnosis.
 ...
PMID:Desmoplastic small round cell tumor: a clinicopathologic, immunohistochemical, and molecular study of 32 tumors. 1213 Nov 50

The Wilms tumor suppressor gene, WT1, plays an important role in the development of the urogenital system and the gonads, and clinical syndromes associated with WT1 mutations, such as WAGR syndrome, Denys-Drash syndrome and Frasier syndrome, typically manifest as renal and genitourinary abnormalities. WT1 may also play an important role in the development of the diaphragm, and recently several papers have reported an association between WT1 mutations and diaphragmatic hernias. In addition, WT1 mutations were also detected in some patients with Meacham syndrome, a rare malformation syndrome comprising congenital diaphragmatic hernia, double vagina, sex reversal, and cardiac malformations. Here, we report a case of an infant with typical clinical features of Deny-Drash syndrome and a heterozygous missense mutation, Arg366His, in the WT1 gene, in whom a diaphragm defect was detected after starting peritoneal dialysis. Diaphragmatic defects are rare but may be considered as clinical manifestations of WT1 mutation syndromes. In addition, we suggest that WT1 abnormalities should be suspected in patients with chronic renal failure who develop hydrothorax after peritoneal dialysis, especially in those with genitourinary abnormalities.
 ...
PMID:Hydrothorax in a patient with Denys-Drash syndrome associated with a diaphragmatic defect. 1693 93

Congenital diaphragmatic hernia (CDH) is a disorder of the development of the lung and diaphragm and is associated with pulmonary hypoplasia and pulmonary hypertension. Denys-Drash syndrome (DDS) is a well-known syndrome caused by several different germline mutations in the WT1-gene. CDH in DDS is rare. We present the third case of CDH with clinical features of DDS and the same, rare Arg366His mutation in the WT1-gene, as reported in the other two known cases. This report provides additional evidence that WT1 mutations can result in diaphragmatic hernia.
 ...
PMID:Denys-Drash syndrome and congenital diaphragmatic hernia: another case with the 1097G > A(Arg366His) mutation. 1820 54

Inguinal hernia repair is one of the most commonly performed operations in the world, yet little is known about the genetic mechanisms that predispose individuals to develop inguinal hernias. We perform a genome-wide association analysis of surgically confirmed inguinal hernias in 72,805 subjects (5,295 cases and 67,510 controls) and confirm top associations in an independent cohort of 92,444 subjects with self-reported hernia repair surgeries (9,701 cases and 82,743 controls). We identify four novel inguinal hernia susceptibility loci in the regions of EFEMP1, WT1, EBF2 and ADAMTS6. Moreover, we observe expression of all four genes in mouse connective tissue and network analyses show an important role for two of these genes (EFEMP1 and WT1) in connective tissue maintenance/homoeostasis. Our findings provide insight into the aetiology of hernia development and highlight genetic pathways for studies of hernia development and its treatment.
...
PMID:A genome-wide association study identifies four novel susceptibility loci underlying inguinal hernia. 2668 53

Congenital diaphragmatic hernia (CDH) is a severe birth defect. Wt1-null mouse embryos develop CDH but the mechanisms regulated by WT1 are unknown. We have generated a murine model with conditional deletion of WT1 in the lateral plate mesoderm, using the G2 enhancer of the Gata4 gene as a driver. 80% of G2-Gata4(Cre);Wt1(fl/fl) embryos developed typical Bochdalek-type CDH. We show that the posthepatic mesenchymal plate coelomic epithelium gives rise to a mesenchyme that populates the pleuroperitoneal folds isolating the pleural cavities before the migration of the somitic myoblasts. This process fails when Wt1 is deleted from this area. Mutant embryos show Raldh2 downregulation in the lateral mesoderm, but not in the intermediate mesoderm. The mutant phenotype was partially rescued by retinoic acid treatment of the pregnant females. Replacement of intermediate by lateral mesoderm recapitulates the evolutionary origin of the diaphragm in mammals. CDH might thus be viewed as an evolutionary atavism.
 ...
PMID:Conditional deletion of WT1 in the septum transversum mesenchyme causes congenital diaphragmatic hernia in mice. 2764 10