Brief Summary

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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.

• Study Type: Observational
• Study Design: Observational Model: Case-Only, Time Perspective: Cross-Sectional

Interventions Used in this Clinical Trial

• Genetic: mitochondrial DNA mutations diagnosis
  • Identification of large-scale mutations of POLG gene by QMPSF in patients with mitochondrial DNA instability.

Arms, Groups and Cohorts in this Clinical Trial

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

Outcome Measures for this Clinical Trial

Primary Measures

• Improving the diagnosis of mitochondrial pathology
  • Time Frame: 1 day
    Safety Issue?: No

Criteria for Participation in this Clinical Trial

Inclusion Criteria

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

• Lead Sponsor
  • Centre Hospitalier Universitaire de Nice
• Provider of Information About this Clinical Study
  • Centre Hospitalier Universitaire de Nice, Département de la Recherche Clinique et de l'Innovation
• Overall Official(s)
  • Cécile ROUZIER, MD, Principal Investigator, Centre Hospitalier Universitaire
• Overall Contact(s)
  • Cécile ROUZIER, MD, 00-33(0)4.92.03.64.59, rouzier.c@chu-nice.fr