Characterization of the Interruptions of the GAA Expansion and Study of Their Influence on the Severity of Friedreich's Ataxia

NCT04346238 | Completed

• 1 other identifier: RECHMPL20_0029
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Friedreich's ataxia (FA) is the most frequent recessive genetic ataxia with an estimated prevalence of 1/50 000. The first symptoms appear around the age of 10 years with a progressive course and the need for an armchair 10- 15 years after the first symptoms. More rarely the disease can present with a late onset (after the age of 25) with a picture characterized by spastic paraparesis and slower progression ("LOFA" for "Late Onset Friedreich Ataxia" or VLOFA for "Very Late Appearance of Friedreich's ataxia "). AF is caused in 96% of cases by an expansion of GAAN triplets (N\> 100 repeats) located in intron 1 of the FXN gene, present on the two alleles, and, in the rest of the cases, by an associated expansion a point mutation or a deletion in trans. During molecular diagnostics, it is not uncommon to find the presence of interruptions within the GAA expansion. This results in the absence and / or the shift of peak (s) within the chromatogram. To date, only the partial correlation between the size of the expansion and the age of onset of Friedreich's ataxia has been established. In particular, very atypical forms of AF with a late onset (after the age of 25) are in particular explained by the low number of repetitions in the expansion, typically between 100 and 500 repetitions. However, the presence of an interruption could stabilize the size of the expansion and, therefore, be mainly associated with expansions of small sizes and therefore with a late onset of the disease. The objective of this study is therefore to analyse and caracterize the presence and the type of interruptions of the GAA expansions in a group of patients with FA ; this data will be correlated with the age at onset of FA.

Conditions

Friedreich Ataxia

Keywords

Neurology; Genetic; Friedreich ataxia

Outcome Measures

Primary Outcomes (1)

• Interruptions and date at onset

  Study the correlation between the presence and type of interruptions (location within the expansion, nucleotide sequence: "GAAA", "GAG", etc.) and the age of onset of Friedreich's ataxia.

  18 months

Secondary Outcomes (1)

• Clinical correlation

  18 months

Study Arms (1)

Patients with Friedriech Ataxia genetically confirmed

Patients with Friedriech Ataxia genetically confirmed

Other: Reuse of existing data from patients' medical records

Interventions

Reuse of existing data from patients' medical records OTHER

Reuse of existing data from patients' medical records

Patients with Friedriech Ataxia genetically confirmed

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with Friedriech Ataxia genetically confirmed. .

You may qualify if:

• Subjects with diagnosis of genetically confirmed Friedreich's Ataxia (AF) and :
• two expansions of GAAN triplets (\> 100 repetitions or "premutation", corresponding to\> 32 but \<100 repetitions) located in intron 1 of the FXN gene present on the two alleles;
• symptomatic (SARA scale\> 4);
• having signed a consent for the performance of genetic analyzes which also includes the authorization for the conduct of further studies for research purposes and the authorization for the collection, entry and computer processing of medical data, in all confidentiality. A newsletter on the principle of non-opposition will be sent.

You may not qualify if:

• Patients with Friedreich's ataxia due to an expansion associated with a point mutation or a deletion in trans;
• Patients who, at the time of signing the genetic consent, objected to the use of their data for research purposes.

Sponsors & Collaborators

• Genetic Department , CHU Montpellier-France: collaborator
• Neurology department, CHU La réunion: collaborator
• Neurogenetic department, CHU Bordeaux: collaborator
• University Hospital, Montpellier: lead

Study Sites (1)

Uh Montpellier

Montpellier, Montpellier, 34295, France

Location

Related Publications (1)

• Benkirane M, Marelli C, Choumert A, Goizet C, Patat O, Ewenczyk C, Anheim M, Megarbane A, Larrieu L, Charlin C, Ory-Magne F, Chaussenot A, Fradin M, Guissart C, Pointaux M, Cossee M, Vincent MC, Bergougnoux A, Hersent C, Bareil C, Roubertie A, Fluchere F, Renaud M, Kremer L, Tranchant C, Attarian S, Odent S, Laugel V, Walther-Louvier U, Desnous B, Bieth E, Husson I, Azulay JP; INTREP-AF consortium; Rivier F, Doray B, Durr A, Aouinti S, Molinari N, Koenig M. Type and position of repeat interruptions as determinants of disease severity and expansion size in Friedreich ataxia. Genet Med. 2025 Dec;27(12):101588. doi: 10.1016/j.gim.2025.101588. Epub 2025 Sep 23.

  PMID: 41014100 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

NC

MeSH Terms

Conditions

Friedreich Ataxia

Condition Hierarchy (Ancestors)

Spinocerebellar Degenerations; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Mitochondrial Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Cecilia Marelli, MD

  University Hospitals of Montpellier

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2020
• First Posted: April 15, 2020
• Study Start: March 1, 2020
• Primary Completion: March 30, 2024
• Study Completion: December 1, 2024
• Last Updated: June 2, 2026

Record last verified: 2026-05

Locations

FR (1)