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

NCT ID: NCT00831948

Last Updated: 2009-01-29

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 20 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2008-12-31

Brief Summary

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.

Conditions

Mitochondrial Diseases; Diagnosis; DNA Mutations

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

Mitochondrial disease

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

mitochondrial DNA mutations diagnosis

Intervention Type: GENETIC

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

Interventions

mitochondrial DNA mutations diagnosis

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

Intervention Type: GENETIC

Eligibility Criteria

Inclusion Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: lead

Responsible Party

Département de la Recherche Clinique et de l'Innovation

Principal Investigators

Cécile ROUZIER, MD

Role: PRINCIPAL_INVESTIGATOR

Centre Hospitalier Universitaire

Locations

Centre Hospitalier Universitaire de Nice- Hôpital ARCHET 2 -Laboratoire de Génétique Médicale

Nice, , France

Site Status: RECRUITING

Countries

France

Central Contacts

Cécile ROUZIER, MD

Role: CONTACT

rouzier.c@chu-nice.fr

00-33(0)4.92.03.64.59

Facility Contacts

Cécile ROUZIER, MD

Role: primary

rouzier.c@chu-nice.fr

00-33 (0)4.92.03.64.59

Other Identifiers

08-CIR-02- Dr ROUZIER

Identifier Type: -

Identifier Source: org_study_id