A Nonsense Mutation in COQ9 Causes Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q10 Deficiency: A Potentially Treatable Form of Mitochondrial Disease
Identifieur interne : 000995 ( Ncbi/Curation ); précédent : 000994; suivant : 000996A Nonsense Mutation in COQ9 Causes Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q10 Deficiency: A Potentially Treatable Form of Mitochondrial Disease
Auteurs : Andrew J. Duncan ; Maria Bitner-Glindzicz ; Brigitte Meunier ; Harry Costello ; Iain P. Hargreaves ; Luis C. L Pez ; Michio Hirano ; Catarina M. Quinzii ; Michael I. Sadowski ; John Hardy ; Andrew Singleton ; Peter T. Clayton ; Shamima RahmanSource :
- American Journal of Human Genetics [ 0002-9297 ] ; 2009.
Abstract
Coenzyme Q10 is a mobile lipophilic electron carrier located in the inner mitochondrial membrane. Defects of coenzyme Q10 biosynthesis represent one of the few treatable mitochondrial diseases. We genotyped a patient with primary coenzyme Q10 deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction. Cultured skin fibroblasts from the patient had a coenzyme Q10 biosynthetic rate of 11% of normal controls and accumulated an abnormal metabolite that we believe to be a biosynthetic intermediate. In view of the rarity of coenzyme Q10 deficiency, we hypothesized that the disease-causing gene might lie in a region of ancestral homozygosity by descent. Data from an Illumina HumanHap550 array were analyzed with BeadStudio software. Sixteen regions of homozygosity >1.5 Mb were identified in the affected infant. Two of these regions included the loci of two of 16 candidate genes implicated in human coenzyme Q10 biosynthesis. Sequence analysis demonstrated a homozygous stop mutation affecting a highly conserved residue of
Url:
DOI: 10.1016/j.ajhg.2009.03.018
PubMed: 19375058
PubMed Central: 2681001
Links toward previous steps (curation, corpus...)
- to stream Pmc, to step Corpus: Pour aller vers cette notice dans l'étape Curation :000424
- to stream Pmc, to step Curation: Pour aller vers cette notice dans l'étape Curation :000421
- to stream Pmc, to step Checkpoint: Pour aller vers cette notice dans l'étape Curation :000832
- to stream Ncbi, to step Merge: Pour aller vers cette notice dans l'étape Curation :000995
Links to Exploration step
PMC:2681001Le document en format XML
<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Nonsense Mutation in <italic>COQ9</italic>
Causes Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q<sub>10</sub>
Deficiency: A Potentially Treatable Form of Mitochondrial Disease</title>
<author><name sortKey="Duncan, Andrew J" sort="Duncan, Andrew J" uniqKey="Duncan A" first="Andrew J." last="Duncan">Andrew J. Duncan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bitner Glindzicz, Maria" sort="Bitner Glindzicz, Maria" uniqKey="Bitner Glindzicz M" first="Maria" last="Bitner-Glindzicz">Maria Bitner-Glindzicz</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meunier, Brigitte" sort="Meunier, Brigitte" uniqKey="Meunier B" first="Brigitte" last="Meunier">Brigitte Meunier</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Costello, Harry" sort="Costello, Harry" uniqKey="Costello H" first="Harry" last="Costello">Harry Costello</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hargreaves, Iain P" sort="Hargreaves, Iain P" uniqKey="Hargreaves I" first="Iain P." last="Hargreaves">Iain P. Hargreaves</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="L Pez, Luis C" sort="L Pez, Luis C" uniqKey="L Pez L" first="Luis C." last="L Pez">Luis C. L Pez</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hirano, Michio" sort="Hirano, Michio" uniqKey="Hirano M" first="Michio" last="Hirano">Michio Hirano</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Quinzii, Catarina M" sort="Quinzii, Catarina M" uniqKey="Quinzii C" first="Catarina M." last="Quinzii">Catarina M. Quinzii</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sadowski, Michael I" sort="Sadowski, Michael I" uniqKey="Sadowski M" first="Michael I." last="Sadowski">Michael I. Sadowski</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<affiliation><nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Clayton, Peter T" sort="Clayton, Peter T" uniqKey="Clayton P" first="Peter T." last="Clayton">Peter T. Clayton</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rahman, Shamima" sort="Rahman, Shamima" uniqKey="Rahman S" first="Shamima" last="Rahman">Shamima Rahman</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9"></nlm:aff>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">19375058</idno>
<idno type="pmc">2681001</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681001</idno>
<idno type="RBID">PMC:2681001</idno>
<idno type="doi">10.1016/j.ajhg.2009.03.018</idno>
<date when="2009">2009</date>
<idno type="wicri:Area/Pmc/Corpus">000424</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000424</idno>
<idno type="wicri:Area/Pmc/Curation">000421</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000421</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000832</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000832</idno>
<idno type="wicri:Area/Ncbi/Merge">000995</idno>
<idno type="wicri:Area/Ncbi/Curation">000995</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">A Nonsense Mutation in <italic>COQ9</italic>
Causes Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q<sub>10</sub>
Deficiency: A Potentially Treatable Form of Mitochondrial Disease</title>
<author><name sortKey="Duncan, Andrew J" sort="Duncan, Andrew J" uniqKey="Duncan A" first="Andrew J." last="Duncan">Andrew J. Duncan</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Bitner Glindzicz, Maria" sort="Bitner Glindzicz, Maria" uniqKey="Bitner Glindzicz M" first="Maria" last="Bitner-Glindzicz">Maria Bitner-Glindzicz</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Meunier, Brigitte" sort="Meunier, Brigitte" uniqKey="Meunier B" first="Brigitte" last="Meunier">Brigitte Meunier</name>
<affiliation><nlm:aff id="aff2"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Costello, Harry" sort="Costello, Harry" uniqKey="Costello H" first="Harry" last="Costello">Harry Costello</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hargreaves, Iain P" sort="Hargreaves, Iain P" uniqKey="Hargreaves I" first="Iain P." last="Hargreaves">Iain P. Hargreaves</name>
<affiliation><nlm:aff id="aff3"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="L Pez, Luis C" sort="L Pez, Luis C" uniqKey="L Pez L" first="Luis C." last="L Pez">Luis C. L Pez</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hirano, Michio" sort="Hirano, Michio" uniqKey="Hirano M" first="Michio" last="Hirano">Michio Hirano</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Quinzii, Catarina M" sort="Quinzii, Catarina M" uniqKey="Quinzii C" first="Catarina M." last="Quinzii">Catarina M. Quinzii</name>
<affiliation><nlm:aff id="aff4"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Sadowski, Michael I" sort="Sadowski, Michael I" uniqKey="Sadowski M" first="Michael I." last="Sadowski">Michael I. Sadowski</name>
<affiliation><nlm:aff id="aff5"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Hardy, John" sort="Hardy, John" uniqKey="Hardy J" first="John" last="Hardy">John Hardy</name>
<affiliation><nlm:aff id="aff6"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Singleton, Andrew" sort="Singleton, Andrew" uniqKey="Singleton A" first="Andrew" last="Singleton">Andrew Singleton</name>
<affiliation><nlm:aff id="aff7"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Clayton, Peter T" sort="Clayton, Peter T" uniqKey="Clayton P" first="Peter T." last="Clayton">Peter T. Clayton</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
</author>
<author><name sortKey="Rahman, Shamima" sort="Rahman, Shamima" uniqKey="Rahman S" first="Shamima" last="Rahman">Shamima Rahman</name>
<affiliation><nlm:aff id="aff1"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff8"></nlm:aff>
</affiliation>
<affiliation><nlm:aff id="aff9"></nlm:aff>
</affiliation>
</author>
</analytic>
<series><title level="j">American Journal of Human Genetics</title>
<idno type="ISSN">0002-9297</idno>
<idno type="eISSN">1537-6605</idno>
<imprint><date when="2009">2009</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p>Coenzyme Q<sub>10</sub>
is a mobile lipophilic electron carrier located in the inner mitochondrial membrane. Defects of coenzyme Q<sub>10</sub>
biosynthesis represent one of the few treatable mitochondrial diseases. We genotyped a patient with primary coenzyme Q<sub>10</sub>
deficiency who presented with neonatal lactic acidosis and later developed multisytem disease including intractable seizures, global developmental delay, hypertrophic cardiomyopathy, and renal tubular dysfunction. Cultured skin fibroblasts from the patient had a coenzyme Q<sub>10</sub>
biosynthetic rate of 11% of normal controls and accumulated an abnormal metabolite that we believe to be a biosynthetic intermediate. In view of the rarity of coenzyme Q<sub>10</sub>
deficiency, we hypothesized that the disease-causing gene might lie in a region of ancestral homozygosity by descent. Data from an Illumina HumanHap550 array were analyzed with BeadStudio software. Sixteen regions of homozygosity >1.5 Mb were identified in the affected infant. Two of these regions included the loci of two of 16 candidate genes implicated in human coenzyme Q<sub>10</sub>
biosynthesis. Sequence analysis demonstrated a homozygous stop mutation affecting a highly conserved residue of <italic>COQ9</italic>
, leading to the truncation of 75 amino acids. Site-directed mutagenesis targeting the equivalent residue in the yeast <italic>Saccharomyces cerevisiae</italic>
abolished respiratory growth.</p>
</div>
</front>
</TEI>
</record>
Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Sante/explor/ParkinsonFranceV1/Data/Ncbi/Curation
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000995 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd -nk 000995 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien |wiki= Wicri/Sante |area= ParkinsonFranceV1 |flux= Ncbi |étape= Curation |type= RBID |clé= PMC:2681001 |texte= A Nonsense Mutation in COQ9 Causes Autosomal-Recessive Neonatal-Onset Primary Coenzyme Q10 Deficiency: A Potentially Treatable Form of Mitochondrial Disease }}
Pour générer des pages wiki
HfdIndexSelect -h $EXPLOR_AREA/Data/Ncbi/Curation/RBID.i -Sk "pubmed:19375058" \ | HfdSelect -Kh $EXPLOR_AREA/Data/Ncbi/Curation/biblio.hfd \ | NlmPubMed2Wicri -a ParkinsonFranceV1
This area was generated with Dilib version V0.6.29. |