Linked Life Data

10679943

Source:http://linkedlifedata.com/resource/pubmed/id/10679943

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2000-5-4
pubmed:abstractText
The infantile form of neuronal ceroid lipofuscinosis (INCL; CLN1) is the earliest onset form of the neuronal ceroid lipofuscinoses (NCL), a group of progressive encephalopathies of children. INCL is caused by mutations in the palmitoyl protein thioesterase (PPT) gene, and we report here eight novel INCL mutations in PPT. Five of the mutations, c.456C>A, c.162-163insA, c.174-175delG, c.774-775insA, and a splice acceptor mutation IVS1-2A>G in intron 1, caused the generation of a premature STOP codon either directly or after a frameshift. One mutation was a three-bp insertion in exon 2 (c. 132-133insTGT) leading to insertion of one extra cysteine (Ser44-insCys-Cys45), and another mutation, a 3-bp deletion in exon 3 (c.249-251delCTT), led to deletion of Phe84 in PPT. A splice acceptor mutation IVS6-1G>T in intron 6 can be predicted to cause skipping of exon 7 in PPT. All of these novel mutations were associated with the classical phenotype of INCL, with the first symptoms starting around 12 months of age. The severe phenotypes could be explained by the nature of the novel mutations: five are predicted to lead to premature translational termination, thus abolishing the active site of PPT, and three will probably cause a misfolding of the nascent polypeptide. Thirty-five percent (7/20) of the disease alleles in these 11 families contained the most prevalent c.451C>T missense mutation outside Finland [Das et al., 1998]. Consequently, 31 different mutations underlying INCL have been found so far, the majority leading to classical INCL.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1059-7794
pubmed:author
pubmed:copyrightInfo
Copyright 2000 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1).
pubmed:affiliation
National Public Health Institute, Department of Human Molecular Genetics, Helsinki, Finland.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't