Linked Life Data

10556299

Source:http://linkedlifedata.com/resource/pubmed/id/10556299

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
13
pubmed:dateCreated
2000-1-24
pubmed:abstractText
Infantile nephropathic cystinosis is a rare, autosomal recessive disease caused by a defect in the transport of cystine across the lysosomal membrane and characterized by early onset of renal proximal tubular dysfunction. Late-onset cystinosis, a rarer form of the disorder, is characterized by onset of symptoms between 12 and 15 years of age. We previously characterized the cystinosis gene, CTNS, and identified pathogenic mutations in patients with infantile nephropathic cystinosis, including a common, approximately 65 kb deletion which encompasses exons 1-10. Structure predictions suggested that the gene product, cystinosin, is a novel integral lysosomal membrane protein. We now examine the predicted effect of mutations on this model of cystinosin. In this study, we screened patients with infantile nephropathic cystinosis, those with late-onset cystinosis and patients whose phenotype does not fit the classical definitions. We found 23 different mutations in CTNS; 14 are novel mutations. Out of 25 patients with infantile nephropathic cystinosis, 12 have two severely truncating mutations, which is consistent with a loss of functional protein, and 13 have missense or in-frame deletions, which would result in disruption of transmembrane domains and loss of protein function. Mutations found in two late-onset patients affect functionally unimportant regions of cystinosin, which accounts for their milder phenotype. For three patients, the age of onset of cystinosis was <7 years but the course of the disease was milder than the infantile nephropathic form. This suggests that the missense mutations found in these individuals allow production of functional protein and may also indicate regions of cystinosin which are not functionally important.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2507-14
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10556299-Age of Onset, pubmed-meshheading:10556299-Amino Acid Transport Systems, Neutral, pubmed-meshheading:10556299-Cystinosis, pubmed-meshheading:10556299-DNA Mutational Analysis, pubmed-meshheading:10556299-Exons, pubmed-meshheading:10556299-Glycoproteins, pubmed-meshheading:10556299-Haplotypes, pubmed-meshheading:10556299-Humans, pubmed-meshheading:10556299-Membrane Proteins, pubmed-meshheading:10556299-Membrane Transport Proteins, pubmed-meshheading:10556299-Microsatellite Repeats, pubmed-meshheading:10556299-Models, Molecular, pubmed-meshheading:10556299-Phenotype, pubmed-meshheading:10556299-Point Mutation, pubmed-meshheading:10556299-Polymorphism, Single-Stranded Conformational, pubmed-meshheading:10556299-RNA, Messenger, pubmed-meshheading:10556299-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
1999
pubmed:articleTitle
Severity of phenotype in cystinosis varies with mutations in the CTNS gene: predicted effect on the model of cystinosin.
pubmed:affiliation
Nephrourology Unit, Institute of Child Health, University College London Medical School, 30 Guilford Street, London WC1N 1EH, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't