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

Beckwith-Wiedemann syndrome (BWS) is a rare disorder characterized by overgrowth and predisposition to embryonal tumors. BWS is caused by various epigenetic and/or genetic alterations that dysregulate the imprinted genes on chromosome region 11p15.5. Molecular analysis is required to reinforce the clinical diagnosis of BWS and to identify BWS patients with cancer susceptibility. This is particularly crucial prenatally because most signs of BWS cannot be recognized in utero. We established a reliable molecular assay by pyrosequencing to quantitatively evaluate the methylation profiles of ICR1 and ICR2. We explored epigenotype-phenotype correlations in 19 patients that fulfilled the clinical diagnostic criteria for BWS, 22 patients with suspected BWS, and three fetuses with omphalocele. Abnormal methylation was observed in one prenatal case and 19 postnatal cases, including seven suspected BWS. Seven cases showed ICR1 hypermethylation, five cases showed ICR2 hypomethylation, and eight cases showed abnormal methylation of ICR1 and ICR2 indicating paternal uniparental disomy (UPD). More cases of ICR1 alterations and UPD were found than expected. This is likely due to the sensitivity of this approach, which can detect slight deviations in methylation from normal levels. There was a significant correlation (p<0.001) between the percentage of ICR1 methylation and BWS features: severe hypermethylation (range: 75-86%) was associated with macroglossia, macrosomia, and visceromegaly, whereas mild hypermethylation (range: 55-59%) was associated with umbilical hernia and diastasis recti. Evaluation of ICR1 and ICR2 methylation by pyrosequencing in BWS can improve epigenotype-phenotype correlations, detection of methylation alterations in suspected cases, and identification of UPD.
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PMID:Quantitative DNA methylation analysis improves epigenotype-phenotype correlations in Beckwith-Wiedemann syndrome. 2391 91

Background: Congenital diaphragmatic hernia (CDH) is a rare defect of the diaphragm commonly associated with high morbidity and mortality due to lung hypoplasia and pulmonary hypertension. Although in 70% of patients the etiology of a CDH remains unknown, a multitude of causative chromosomal aberrations has been identified. Case presentation: We describe the first case of isolated 11p15 duplication with CDH. The 18.6 Mb large duplication affected 285 RefSeq genes and included the Beckwith-Wiedemann (BWS)-associated imprinting control region 2 (ICR2, KCNQ1OT1 TSS DMR), whereas the ICR1 (H19 TSS DMR) was not affected. We were able to demonstrate de novo occurrence of the duplication. The paternal origin of the chromosomal material was detected by methylation testing the ICR2. Corresponding to other patients with duplications of the paternal ICR2 copy, a BWS phenotype is not present. Conclusions: The patient presented here together with the review of four other cases from the literature indicate an association between duplications of the chromosomal region 11p15 and developmental defects of the diaphragm. Thus, we suggest duplications of 11p15 as a rare cause of CDH. This association may or may not appear in the context of BWS depending on the extent of the duplication and the imprinting status. Hence, a genetic workup should be performed in patients with CDH, particularly when other abnormalities are noted.
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PMID:De Novo Duplication of 11p15 Associated With Congenital Diaphragmatic Hernia. 2992 38