Linked Life Data

10190325

Source:http://linkedlifedata.com/resource/pubmed/id/10190325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-4-20
pubmed:abstractText
Holocarboxylase synthetase deficiency (HCS) is an autosomal recessive disorder characterized by metabolic ketoacidosis, abnormal urine organic metabolites, and dermatitis. These symptoms are improved by pharmacological doses of biotin. In this study, we have analyzed seven patients with HCS deficiency found in European and Middle Eastern countries by using reverse transcription/polymerase chain reaction/single-stranded conformation polymorphism and a sequencing analysis. Although we had previously reported that two mutations were frequent in Japanese patients, no frequent mutations were found in the patients analyzed in this study. Seven novel mutations were identified in the cDNA of the patients; these included three missense mutations, two single-base deletions that resulted in a termination codon, a three-base in-frame deletion, and a 68-bp deletion. A new polymorphism C1121T was also identified in four alleles. A transient expression study demonstrated that the HCS activities of three missense mutations and one amino acid deletion were 1%-14% that of wild-type cDNA; in contrast, the activities of the two single-base deletions followed by a termination codon and Asp571Asn were nearly undetectable. These data suggest that a variety of mutations is responsible for decreasing HCS activity and that the aspartate residue at amino acid position 571 may be crucial for the catalytic activity of HCS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0340-6717
pubmed:author
pubmed:issnType
Print
pubmed:volume
104
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
143-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Identification and characterization of mutations in patients with holocarboxylase synthetase deficiency.
pubmed:affiliation
Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't