Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.

The recruitment status of this study is unknown because the information has not been verified recently.
Verified January 2009 by Centre Hospitalier Universitaire de Nice.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT00831948
First received: January 28, 2009
Last updated: NA
Last verified: January 2009
History: No changes posted
  Purpose

Mitochondrial diseases are a heterogeneous group caused by genetic defects in mitochondrial DNA or in nuclear genes. POLG is the most frequently involved gene in mtDNA instability diseases resulting in mtDNA multiple deletion and/or depletion. It encodes the DNA polymerase gamma (POLγ), the only known DNA polymerase found in mammalian mitochondria. Mutations in POLG could explain 45% of familial progressive external ophtalmoplegia associated with multiple mtDNA deletions. However, in more than 70%, the analysis of the genes involved in mtDNA instability remains unsuccessful.

To date, these genes are screened by sequencing methods that are not able to detect large-scale rearrangements. In order to detect possible large-scale rearrangements, the investigators propose to develop a new assay based on QMPSF (Quantitative Multiplex PCR of Short fluorescent Fragments) able to detect exon deletions and duplications. the investigators propose to screen the POLG gene by QMPSF in at least twenty patients with either no mutation or only one mutation detected in POLG and no mutation in other genes such as TWINKLE and ANT1.

This study would allow the investigators to know if large-scale rearrangements occur in the POLG gene and to estimate their frequency in patients with mtDNA instability. These data are important to know if the sequencing analysis of POLG should be completed by the screening for partial deletions and duplications to ensure an accurate molecular diagnosis of these syndromes. Moreover, this method could be extended to ANT1 and TWINKLE genes.


Condition Intervention
Mitochondrial Diseases
Diagnosis
DNA Mutations
Genetic: mitochondrial DNA mutations diagnosis

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Cross-Sectional
Official Title: Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

Primary Outcome Measures:
  • Improving the diagnosis of mitochondrial pathology [ Time Frame: 1 day ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: December 2008
Groups/Cohorts Assigned Interventions
Mitochondrial disease
Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet detected by current diagnostic techniques
Genetic: mitochondrial DNA mutations diagnosis
Identification of large-scale mutations of POLG gene by QMPSF in patients with mitochondrial DNA instability.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet detected by current diagnostic techniques

Criteria

Inclusion Criteria:

  • Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet detected by current diagnostic techniques
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00831948

Contacts
Contact: Cécile ROUZIER, MD 00-33(0)4.92.03.64.59 rouzier.c@chu-nice.fr

Locations
France
Centre Hospitalier Universitaire de Nice- Hôpital ARCHET 2 -Laboratoire de Génétique Médicale Recruiting
Nice, France, 06200
Contact: Cécile ROUZIER, MD    00-33 (0)4.92.03.64.59    rouzier.c@chu-nice.fr   
Principal Investigator: Cécile ROUZIER, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice
Investigators
Principal Investigator: Cécile ROUZIER, MD Centre Hospitalier Universitaire
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nice, Département de la Recherche Clinique et de l'Innovation
ClinicalTrials.gov Identifier: NCT00831948     History of Changes
Other Study ID Numbers: 08-CIR-02- Dr ROUZIER
Study First Received: January 28, 2009
Last Updated: January 28, 2009
Health Authority: France: French Data Protection Authority

Additional relevant MeSH terms:
Mitochondrial Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on July 22, 2014