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

January 28, 2009 updated by: Centre Hospitalier Universitaire de Nice

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Anticipated)

20

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Nice, France, 06200
        • Recruiting
        • Centre Hospitalier Universitaire de Nice- Hôpital ARCHET 2 -Laboratoire de Génétique Médicale
        • Contact:
        • Principal Investigator:
          • Cécile ROUZIER, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Only
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Improving the diagnosis of mitochondrial pathology
Time Frame: 1 day
1 day

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Centre Hospitalier Universitaire de Nice

Investigators

  • Principal Investigator: Cécile ROUZIER, MD, Centre Hospitalier Universitaire

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Study Registration Dates

First Submitted

January 28, 2009

First Submitted That Met QC Criteria

January 28, 2009

First Posted (Estimate)

January 29, 2009

Study Record Updates

Last Update Posted (Estimate)

January 29, 2009

Last Update Submitted That Met QC Criteria

January 28, 2009

Last Verified

January 1, 2009

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08-CIR-02- Dr ROUZIER

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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