Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
ADCK3, an Ancestral Kinase, Is Mutated in a Form of Recessive Ataxia Associated with Coenzyme Q
10
Deficiency
American Journal of Human Genetics, Volume 82, No. 3, Year 2008
Notification
URL copied to clipboard!
Description
Muscle coenzyme Q10 (CoQ10 or ubiquinone) deficiency has been identified in more than 20 patients with presumed autosomal-recessive ataxia. However, mutations in genes required for CoQ10 biosynthetic pathway have been identified only in patients with infantile-onset multisystemic diseases or isolated nephropathy. Our SNP-based genome-wide scan in a large consanguineous family revealed a locus for autosomal-recessive ataxia at chromosome 1q41. The causative mutation is a homozygous splice-site mutation in the aarF-domain-containing kinase 3 gene (ADCK3). Five additional mutations in ADCK3 were found in three patients with sporadic ataxia, including one known to have CoQ10 deficiency in muscle. All of the patients have childhood-onset cerebellar ataxia with slow progression, and three of six have mildly elevated lactate levels. ADCK3 is a mitochondrial protein homologous to the yeast COQ8 and the bacterial UbiB proteins, which are required for CoQ biosynthesis. Three out of four patients tested showed a low endogenous pool of CoQ10 in their fibroblasts or lymphoblasts, and two out of three patients showed impaired ubiquinone synthesis, strongly suggesting that ADCK3 is also involved in CoQ10 biosynthesis. The deleterious nature of the three identified missense changes was confirmed by the introduction of them at the corresponding positions of the yeast COQ8 gene. Finally, a phylogenetic analysis shows that ADCK3 belongs to the family of atypical kinases, which includes phosphoinositide and choline kinases, suggesting that ADCK3 plays an indirect regulatory role in ubiquinone biosynthesis possibly as part of a feedback loop that regulates ATP production. © 2008 The American Society of Human Genetics.
Authors & Co-Authors
Lagier-Tourenne, Clotilde
France, Paris
Cnrs Centre National de la Recherche Scientifique
Tazir, Mériem
Algeria, Algiers
Centre Hospitalo-universitaire de Mustapha Bacha
López, Luís Carlos
United States, New York
Columbia University Irving Medical Center
Quinzii, Catarina Maria
United States, New York
Columbia University Irving Medical Center
Assoum, Mirna
France, Paris
Cnrs Centre National de la Recherche Scientifique
Drouot, Nathalie
France, Paris
Cnrs Centre National de la Recherche Scientifique
Busso, Cleverson
Brazil, Sao Paulo
Universidade de São Paulo
Makri, Samira
Algeria, Algiers
Etablissement Hospitalier Spécialisé Ali Ait Idir
Ali-Pacha, Lamia
Algeria, Algiers
Centre Hospitalo-universitaire de Mustapha Bacha
Benhassine, Traki
Algeria, Algiers
Institut Pasteur - Alger
Anheim, Mathieu
France, Paris
Cnrs Centre National de la Recherche Scientifique
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Lynch, David R.
United States, Philadelphia
University of Pennsylvania Perelman School of Medicine
Thibault, Christelle
France, Paris
Cnrs Centre National de la Recherche Scientifique
Plewniak, Frédéric
France, Paris
Cnrs Centre National de la Recherche Scientifique
Bianchetti, Laurent
France, Paris
Cnrs Centre National de la Recherche Scientifique
Tranchant, Christine H.
France, Strasbourg
Les Hôpitaux Universitaires de Strasbourg
Poch, Olivier
France, Paris
Cnrs Centre National de la Recherche Scientifique
DiMauro, Salvatore
United States, New York
Columbia University Irving Medical Center
Mandel, Jean Louis
France, Paris
Cnrs Centre National de la Recherche Scientifique
Barros, Mario H.
Brazil, Sao Paulo
Universidade de São Paulo
Hirano, Michio
United States, New York
Columbia University Irving Medical Center
Kœnig, Michel
France, Paris
Cnrs Centre National de la Recherche Scientifique
Statistics
Citations: 301
Authors: 22
Affiliations: 8
Identifiers
Doi:
10.1016/j.ajhg.2007.12.024
ISSN:
00029297
Research Areas
Cancer
Genetics And Genomics
Maternal And Child Health