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

Centre Hospitalier Universitaire de Nice

Status: Unknown

Conditions: DNA Mutations; Diagnosis; Mitochondrial Diseases

Treatments: Genetic: mitochondrial DNA mutations diagnosis

Study type: Observational

Funder types: Other

Identifiers

NCT00831948

08-CIR-02- Dr ROUZIER

Details and patient eligibility

About

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.

Enrollment: 20 estimated patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

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

Trial design

20 participants in 1 patient group

Mitochondrial disease

Description:

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

Treatment:

Genetic: mitochondrial DNA mutations diagnosis