Linked Life Data

11332777

Source:http://linkedlifedata.com/resource/pubmed/id/11332777

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-5-2
pubmed:abstractText
Mutations in the CLN1 gene encoding palmitoyl-protein thioesterase (PPT) underlie the recessive neurodegenerative disorder, infantile Batten disease, or infantile neuronal ceroid lipofuscinosis (INCL). The CLN1 gene was mapped to chromosome 1p32 in the vicinity of a microsatellite marker HY-TM1 in a cohort of Finnish INCL families, and mapping of the PPT gene to the CLN1 critical region (and the discovery of mutations in PPT in several unrelated families) led to conclusive identification of PPT as the disease gene. PPT is a lysosomal thioesterase that removes fatty acids from fatty-acylated cysteine residues in proteins. The accumulation of fatty acyl cysteine thioesters can be reversed in INCL cells by the exogenous administration of recombinant PPT, which enters the cells through the mannose 6-phosphate receptor pathway. Over two dozen PPT mutations have been found in PPT-deficient patients worldwide. In the United States, all PPT-deficient patients show "GROD" histology but the age of onset of symptoms is later in some children due to the presence of missense mutations that result in enzymes with residual PPT activity. Now that INCL is known to be caused by a defect in a soluble lysosomal enzyme, appropriate therapies may be forthcoming. Prospects for therapy include enzyme replacement, stem cell transplantation, gene therapy, and metabolic therapy aimed at depleting the abnormal substrate accumulation in the disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0065-2660
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
69-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Positional candidate gene cloning of CLN1.
pubmed:affiliation
Department of Internal Medicine and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas 75390, USA. hofmann@simmons.swmed.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review