Linked Life Data

10746566

Source:http://linkedlifedata.com/resource/pubmed/id/10746566

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-4-13
pubmed:abstractText
Succinate dehydrogenase (SDH) deficiency represents a minor cause of Leigh syndrome (LS). Noticeably, the first mutation in a nuclear-encoded respiratory chain component, a mutation in the 5p15 copy of the flavoprotein (Fp) subunit gene of the SDH, was reported 4 years ago in two siblings with LS and SDH deficiency. We now report a new patient with LS and SDH deficiency. Because two copies of the Fp gene are present in the human genome, we first determined the complete structure of these two copies. This allowed us to identify a 1 bp deletion creating a frameshift in the 3q29 copy, confirming that this second copy was a pseudogene. We also sequenced the promoter region of the 5p 15 gene and, in addition, screened for mutations in the patient. Sequencing of the Fp SDH cDNA in the patient only allowed us to identify a heterozygous C to T transition, changing an alanine to a valine in one allele. This transition was found to be heterozygous in the patient's father but was absent from 150 controls. Transfection of the corresponding mutant cDNA into human Fp-deficient cells failed to restore normal SDH activity, confirming the deleterious effect of this mutation. The second allele, inherited from the mother, carried an A to C substitution changing the methionine translation initiation codon to a leucine. This mutant transcript represented only 10% of total Fp transcript suggesting instability of this transcript. So far, profound deficiencies in complex II activity resulting from mutations in the Fp gene of the SDH present only as LS, a striking observation in view of the ubiquitous expression of this typical housekeeping gene in humans.
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
106
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
236-43
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome.
pubmed:affiliation
INSERM U393, Hôpital Necker-Enfants-Malades, Paris, France.
pubmed:publicationType
Journal Article