Informations générales (source: ClinicalTrials.gov)
Identification of Large-Scale Mutations of POLG Gene by QMPSF in Patients With Mitochondrial DNA Instability.
Observational
Centre Hospitalier Universitaire de Nice (Voir sur ClinicalTrials)
décembre 2008
29 juin 2024
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.
Etablissements
| Les établissements hors Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| Centre Hospitalier Universitaire de Nice- Hôpital ARCHET 2 -Laboratoire de Génétique Médicale - 06200 - Nice - France | Cécile ROUZIER, MD | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet
detected by current diagnostic techniques
- Patients already diagnosed for mitochondrial pathology without mtDNA mutations yet
detected by current diagnostic techniques