Linked Life Data

10571956

Source:http://linkedlifedata.com/resource/pubmed/id/10571956

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1999-11-30
pubmed:abstractText
Carbohydrate-deficient glycoprotein syndrome type Ia (CDGS) is an autosomal recessive disorder, characterized by a central nervous system dysfunction and multiorgan failure associated with defective N-glycosylation and phosphomannomutase (PMM) deficiency related to mutations in the PMM2 gene. A total of 26 different missense mutations and one single base pair deletion have already been described. We found by sequencing and restriction analysis, in two unrelated French patients with CDG type Ia a compound heterozygosity for two mutations in exon 5: a new mutation 415G>A (E139K) and the most frequent mutation 425G>A (R141H ). The 415G>A mutation disrupted a splicing enhancer sequence: (GAR)n-(GAR)n resulting in exon 5 skipping. We studied the activity of these mutant proteins expressed in E Coli. Compared to the normal PMM protein activity, the R141H and transcript without exon 5 expressed a protein with undetectable specific activity when the E139K mutant protein expressed a residual activity of 25%. The E139K mutant protein could be expressed at a sufficient level in vivo to confer residual activity compatible with life in these patients when absence of residual PMM activity is likely lethal.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1098-1004
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
543-4
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Characterization of the 415G>A (E139K) PMM2 mutation in carbohydrate-deficient glycoprotein syndrome type Ia disrupting a splicing enhancer resulting in exon 5 skipping.
pubmed:affiliation
Biochimie A, Hôpital Bichat-Claude Bernard, 75877-Paris cedex 18, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't