Clinical, Molecular and by Neuroimaging of LRRK2 Mutations (LRRK2)
Clinical, Molecular and by Neuroimaging Characterization of Monogenic Forms of Parkinsonism Syndromes: Mutations of the LRRK2 Gene.
Besides Parkinson's disease (PD), it exists rare parkinsonian syndromes clinically close to PD and that correspond to Mendelian entities. Autosomal dominant forms are mainly associated with mutations of alpha synuclein and LRRK2/dardarin genes, whereas autosomal recessive forms are due to mutations in Parkin, Pink1 and DJ-1 genes. This entities are still unknown on the clinical, genetic and metabolic " au plan ".
Throughout a national network of 15 specialized centres in movement disorders, coordinated by the team of the neurogenetics reference centre at the Pitié-Salpêtrière Hospital (Alexis Brice), we propose to precise the relative frequency, the molecular bases and abnormalities in functional neuroimaging associated with the LRRK2 gene mutations, the most frequently implicated in the autosomal dominant forms. Due to the relative rarity of this parkinsonian syndrome, we will perform at the same time a retrospective study in cases and families already collected by the national network (300 isolated cases and 300 families) and a prospective study. The network will recruit 100 isolated cases and 40 familial cases yearly, with precise diagnosis tools. The genetic analysis will evaluate the relative frequency of the LRRK2 mutations and their spectrum in the French population. Phenotype-genotype correlations will be performed to better orientate the molecular diagnosis, in order to improve the genetic counselling and reduce costs of these analyses. In the case of LRRK2 mutations, a genetic investigation will be proposed to the families, with a specific care to at-risk cases. A detailed phenotypic evaluation of patients and at-risk cases will be proposed (neurological, neuropsychiatric and behavioural) at the CIC Pitié-Salpêtrière and also in imaging, for 15 patients and 40 of their relatives (20 carriers and 20 non-carriers of the LRRK2 mutation). The TEP study will evaluate the dopaminergic function (fluorodopa capture) and will measure the dopamine transporter (DAT). The structural MRI evaluation will search for possible associated structural morphologic abnormalities. The functional MRI evaluation will search for dysfunction of motor circuit during the movement realisation. These examinations will be performed at two years of interval for appreciate the evolution of the disease. This study will allow to better characterize the parkinsonian syndromes due to LRRK2 mutations and also to better characterize the presymptomatic phase, which is subject to controversies in idiopathic PD. The feasibility of this project is assured by the expertise of the collaborative centres and by the inclusion of a retrospective cohort, combined to a prospective cohort, which will allow to recruit sufficient patients and at-risk relatives for a rare genetic entity.
調査の概要
状態
条件
研究の種類
入学 (予想される)
連絡先と場所
研究場所
-
-
-
Orsay、フランス、91401
- 積極的、募集していない
- CEA - Service Hospitalier Frédéric Joliot
-
Paris、フランス、75013
- 募集
- Pitié-Salpêtrière Hospital
-
副調査官:
- Alexandra DURR, MD, PhD
-
コンタクト:
- BRICE
- メール:alexis.brice@upmc.fr
-
副調査官:
- Stéphane Lehéricy, MD, PhD
-
副調査官:
- Jean-Christophe CORVOL, MD, PHD
-
副調査官:
- Isabelle ARNULF, MD, PhD
-
副調査官:
- Yves AGID, MD, PhD
-
副調査官:
- Perrine CHARLES, MD, PhD
-
副調査官:
- Mathieu ANHEIM, MD, PhD
-
副調査官:
- Anne-Marie BONNET, MD
-
副調査官:
- Marie VIDAILHET, MD
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- To be over 18 years old
- Diagnosis of Parkinson's disease
- To be a first-degree relative to a LRRK2 patient
- Ability to understand the aim of the study
- Ability to sign the consent form
Exclusion Criteria:
- Non ability to understand the aim of the study
- Non ability to sign the consent form
- Inability to do a MRI
- Pregnant women or absence of an effective contraception
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 観測モデル:家族ベース
- 時間の展望:見込みのある
コホートと介入
グループ/コホート |
---|
Patients carrier of a LRRK2 mutation
|
Asymptomatic relatives of LRRK2 patients
|
協力者と研究者
研究記録日
主要日程の研究
研究開始
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
パーキンソン病の臨床試験
-
Adelphi Values LLCBlueprint Medicines Corporation完了肥満細胞性白血病 (MCL) | 攻撃的な全身性肥満細胞症 (ASM) | SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD) | くすぶり全身性肥満細胞症 (SSM) | 無痛性全身性肥満細胞症 (ISM) ISM サブグループが完全に募集されましたアメリカ