Characterization of the Interruptions of the GAA Expansion and Study of Their Influence on the Severity of Friedreich's Ataxia : INTREP-AF
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Interruptions and date at onset
研究概览
简要总结
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Retrospective
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Interruptions and date at onset
时间窗: 18 months
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.
次要结局
- Clinical correlation(18 months)