Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
Recruitment status was: Recruiting
|First Submitted Date||January 28, 2009|
|First Posted Date||January 29, 2009|
|Last Update Posted Date||January 29, 2009|
|Start Date||December 2008|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures
||Improving the diagnosis of mitochondrial pathology [ Time Frame: 1 day ]|
|Original Primary Outcome Measures||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures||Not Provided|
|Original Secondary Outcome Measures||Not Provided|
|Current Other Outcome Measures||Not Provided|
|Original Other Outcome Measures||Not Provided|
|Brief Title||Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.|
|Official Title||Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.|
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.
|Detailed Description||Not Provided|
|Study Design||Observational Model: Case-Only
Time Perspective: Cross-Sectional
|Target Follow-Up Duration||Not Provided|
|Sampling Method||Non-Probability Sample|
|Study Population||Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet detected by current diagnostic techniques|
|Intervention||Genetic: mitochondrial DNA mutations diagnosis
Identification of large-scale mutations of POLG gene by QMPSF in patients with mitochondrial DNA instability.
|Study Groups/Cohorts||Mitochondrial disease
Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet detected by current diagnostic techniques
Intervention: Genetic: mitochondrial DNA mutations diagnosis
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status||Unknown status|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Ages||Child, Adult, Senior|
|Accepts Healthy Volunteers||No|
|Contacts||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries||France|
|Removed Location Countries|
|Other Study ID Numbers||08-CIR-02- Dr ROUZIER|
|Has Data Monitoring Committee||No|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Centre Hospitalier Universitaire de Nice, Département de la Recherche Clinique et de l'Innovation|
|Study Sponsor||Centre Hospitalier Universitaire de Nice|
|PRS Account||Centre Hospitalier Universitaire de Nice|
|Verification Date||January 2009|