Linked Life Data

19236432

Source:http://linkedlifedata.com/resource/pubmed/id/19236432

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-5-7
pubmed:abstractText
Mutations in ROR2, encoding a receptor tyrosine kinase, can cause autosomal recessive Robinow syndrome (RRS), a severe skeletal dysplasia with limb shortening, brachydactyly, and a dysmorphic facial appearance. Other mutations in ROR2 result in the autosomal dominant disease, brachydactyly type B (BDB1). No functional mechanisms have been delineated to effectively explain the association between mutations and different modes of inheritance causing different phenotypes. BDB1-causing mutations in ROR2 result from heterozygous premature termination codons (PTCs) in downstream exons and the conveyed phenotype segregates as an autosomal dominant trait, whereas heterozygous missense mutations and PTCs in upstream exons result in carrier status for RRS. Given that the distribution of PTC mutations revealed a correlation between the phenotype and the mode of inheritance conveyed, we investigated the potential role for the nonsense-mediated decay (NMD) pathway in the abrogation of possible aberrant effects of selected mutant alleles. Our experiments show that triggering or escaping NMD may cause different phenotypes with a distinct mode of inheritance. We generalize these findings to other disease-associated genes by examining PTC mutation distribution correlation with conveyed phenotype and inheritance patterns. Indeed, NMD may explain distinct phenotypes and different inheritance patterns conveyed by allelic truncating mutations enabling better genotype-phenotype correlations in several other disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1399-0004
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
75
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
394-400
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Dominant versus recessive traits conveyed by allelic mutations - to what extent is nonsense-mediated decay involved?
pubmed:affiliation
Department of Molecular and Human Genetic, Baylor College of Medicine, Houston, TX 77030, USA.
pubmed:publicationType
Journal Article