UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Tucci A, Liu Y-T, Preza E, Pitceathly RDS, Chalasani A, Plagnol V, Land JM, Trabzuni D, Ryten M, UKBEC , Jaunmuktane Z, Reilly MM, Brandner S, Hargreaves I, Hardy J, Singleton AB, Abramov AY, Houlden H
  • Publication date:
    05/2014
  • Pagination:
    486, 492
  • Journal:
    J Neurol Neurosurg Psychiatry
  • Volume:
    85
  • Issue:
    5
  • Status:
    Published
  • Country:
    England
  • PII:
    jnnp-2013-306387
  • Language:
    eng
  • Keywords:
    Genetics, Neuropathy, Adolescent, Adult, Child, Cohort Studies, Female, GTP Phosphohydrolases, Genotype, Hereditary Sensory and Motor Neuropathy, Humans, Male, Middle Aged, Mitochondrial Proteins, Mutation, Pedigree, Peptide Termination Factors, Polymorphism, Single Nucleotide, Ribose-Phosphate Pyrophosphokinase, Young Adult
Abstract
OBJECTIVE: Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified. METHODS: We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation. Using a variety of methods we investigated the possibility of mitochondrial impairment in the patients cell lines. RESULTS: We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene. We report mitochondrial impairment in the patients cell lines, followed by multiple lines of evidence which include decrease of complex V activity and stability (blue native gel assay), decrease in mitochondrial respiration rate and reduction of mitochondrial membrane potential. CONCLUSIONS: This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Clinical and Movement Neurosciences
Author
Neurodegenerative Diseases
Author
Neurodegenerative Diseases
Author
Department of Neuromuscular Diseases
Author
Department of Neuromuscular Diseases
Author
Genetics, Evolution & Environment
Author
Department of Neuromuscular Diseases
Author
Neurodegenerative Diseases
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by