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)

Congenital diaphragmatic hernia (CDH) has an incidence of 1 in 3,000 births and a high mortality rate (33%-58%). Multifactorial inheritance, teratogenic agents, and genetic abnormalities have all been suggested as possible etiologic factors. To define candidate regions for CDH, we analyzed cytogenetic data collected on 200 CDH cases, of which 7% and 5% showed numerical and structural abnormalities, respectively. This study focused on the most frequent structural anomaly found: a deletion on chromosome 15q. We analyzed material from three of our patients and from four previously published patients with CDH and a 15q deletion. By using array-based comparative genomic hybridization and fluorescent in situ hybridization to determine the boundaries of the deletions and by including data from two individuals with terminal 15q deletions but without CDH, we were able to exclude a substantial portion of the telomeric region from the genetic etiology of this disorder. Moreover, one patient with CDH harbored a small interstitial deletion. Together, these findings allowed us to define a minimal deletion region of approximately 5 Mb at chromosome 15q26.1-26.2. The region contains four known genes, of which two--NR2F2 and CHD2--are particularly intriguing gene candidates for CDH.
 ...
PMID:Congenital diaphragmatic hernia and chromosome 15q26: determination of a candidate region by use of fluorescent in situ hybridization and array-based comparative genomic hybridization. 1625 46

Congenital diaphragmatic hernia (CDH) is a common birth defect with a high mortality and morbidity. There have been few studies that have assessed copy number changes in CDH. We present array comparative genomic hybridization data for 29 CDH patients to identify and map chromosome aberrations in this disease. Three patients with 15q26.1-15q26.2 deletions had heterogeneous breakpoints that overlapped with the critical 4 Mb region previously delineated for CDH, confirming 15q26.1-15q26.2 as a critical region for CDH. The three other most compelling CDH-critical regions for genomic deletions based on these data and a literature review are located at chromosomes 8p23.1, 4p16.3-4pter, and 1q41-1q42.1. Based on these recurrent deletions at 15q26.1-15q26.2, we hypothesized that loss-of-function mutations in a gene or genes from this region could cause CDH and sequenced six candidate genes from this region in more than 100 patients with CDH. For three of these genes (CHD2, ARRDC4, and RGMA), we identified missense changes and that were not identified in normal controls; however, none of these alterations appeared unambiguously causal with CDH. These data suggest that CDH caused by chromosome deletions at 15q26.2 may arise because of a contiguous gene deletion syndrome or may have a multifactorial etiology. In addition, there is evidence for substantial genetic heterogeneity in CDH and diaphragmatic hernias can be non-penetrant in patients who have deletions involving CDH-critical regions.
 ...
PMID:Array comparative genomic hybridization in patients with congenital diaphragmatic hernia: mapping of four CDH-critical regions and sequencing of candidate genes at 15q26.1-15q26.2. 1673 36