Linked Life Data

8526465

Source:http://linkedlifedata.com/resource/pubmed/id/8526465

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1996-1-23
pubmed:abstractText
To correlate genotype with response to early copper histidine therapy in Menkes disease, an X-linked disorder of copper transport, we performed mutational analysis in 2 related males who began treatment at the age of 10 days and prenatally at 32 weeks' gestation, respectively. A G to T transversion at the -1 exonic position of a splice donor site was identified, predicting a glutamine to histidine substitution at codon 724 of the Menkes copper-transporting ATPase gene. The Q724H mutation disrupts proper splicing and generates five mutant transcripts that skip from one to four exons. None of these transcripts is predicted to encode a functional copper transport protein. Copper histidine treatment normalized circulating copper and ceruloplasmin levels but did not improve the baseline deficiency of dopamine-beta-hydroxylase, a copper-dependent enzyme. At the age of 36 months, the first patient was living and had neurodevelopmental abilities ranging from 10 to 15 months. The second patient also showed delayed neurodevelopment and died of pulmonary complications at the age of 5 1/2 months. We conclude that early copper histidine therapy does not normalize neurological outcome in patients with the Q724H splicing mutation, and suggest that preservation of some residual Menkes ATPase activity may be a general prerequisite for significant clinical efficacy from such treatment.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0364-5134
pubmed:author
pubmed:issnType
Print
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
921-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Early copper therapy in classic Menkes disease patients with a novel splicing mutation.
pubmed:affiliation
Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1424, USA.
pubmed:publicationType
Journal Article