Linked Life Data

8896569

Source:http://linkedlifedata.com/resource/pubmed/id/8896569

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-12-16
pubmed:abstractText
Hirschsprung disease (HSCR, aganglionic megacolon) is a common congenital malformation leading to bowel obstruction, with an incidence of 1/5,000 live births. It is characterized by the absence of intrinsic ganglion cells in the myenteric and submucosal plexuses along variable lengths of the gastrointestinal tract. As enteric neurons are derived from the vagal neural crest, HSCR is regarded as a neurocristopathy. On the basis of a skewed sex-ratio (M/F = 4/1) and a risk to relatives much higher than the incidence in the general population, HSCR has long been regarded as a sex-modified multifactorial disorder. Accordingly, segregation analysis suggested an incompletely penetrant dominant inheritance in HSCR families with aganglionosis extending beyond the sigmoid colon. We and others have mapped a dominant gene for HSCR to chromosome 10q11.2 and have ascribed the disease to mutations in the RET proto-oncogene. However, the lack of genotype-phenotype correlation, the low penetrance and the sex-dependent effect of RET mutations supported the existence of one or more modifier gene(s) in familial HSCR. In addition, thus far, RET mutations only accounted for 50% and 15-20% of familial and sporadic HSCR patients, respectively. RET encodes a tyrosine kinase receptor whose ligand was unknown. Recently, the Glial cell line-derived neurotrophic factor (GDNF) has been identified to be a ligand for RET. Moreover, Gdnf-/- knockout mutant mice display congenital intestinal aganglionosis and renal agenesis, a phenotype very similar to the Ret-/- mouse. These data prompted us to hypothesize that mutations of the gene encoding GDNF could either cause or modulate the HSCR phenotype in some cases.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1061-4036
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
345-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:8896569-Drosophila Proteins, pubmed-meshheading:8896569-Female, pubmed-meshheading:8896569-Germ-Line Mutation, pubmed-meshheading:8896569-Glial Cell Line-Derived Neurotrophic Factor, pubmed-meshheading:8896569-Glial Cell Line-Derived Neurotrophic Factor Receptors, pubmed-meshheading:8896569-Hirschsprung Disease, pubmed-meshheading:8896569-Humans, pubmed-meshheading:8896569-Male, pubmed-meshheading:8896569-Nerve Growth Factors, pubmed-meshheading:8896569-Nerve Tissue Proteins, pubmed-meshheading:8896569-Pedigree, pubmed-meshheading:8896569-Phenotype, pubmed-meshheading:8896569-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:8896569-Proto-Oncogene Proteins, pubmed-meshheading:8896569-Proto-Oncogene Proteins c-ret, pubmed-meshheading:8896569-Receptor Protein-Tyrosine Kinases, pubmed-meshheading:8896569-Sequence Analysis, DNA
pubmed:year
1996
pubmed:articleTitle
Germline mutations of the RET ligand GDNF are not sufficient to cause Hirschsprung disease.
pubmed:affiliation
Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-393, Hôpital des Enfants Malades, Institut Necker, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't