Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy
试验速览
- 阶段
- 不适用
- 入组人数
- 240
- 试验地点
- 1
- 主要终点
- Cardiac status
研究概览
简要总结
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation.
The aim of the study is to describe the clinical characteristics of single mutation carriers of recessive myopathy, through measuring serum creatine kinase, muscle strength, muscle degeneration (by MRI) and heart affection. The investigators will do this by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography.
The aim is further to describe whether these characteristics are found primarily with specific mutations.
详细描述
Background:
Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation. This has recently been demonstrated by researchers for the recessively inherited limb girdle muscle dystrophy (LGMD) type 2A, where carriers of single mutations can also be symptomatic. In X-linked recessively inherited dystrophinopathies caused by mutations in the DMD gene on chromosome Xp21, female mutation carriers may also manifest with disease, although this is often milder than affected men. In the recently discovered LGMD2L, manifesting carriers are also suspected. Thus, according to statistics, too many persons evaluated for myopathy carry a single LGMD2L mutation.
Some previous studies have looked into the significance of being a single mutation carrier in recessive muscle disease. In dystrophinopathy, it was reported that 5 % of female DMD carriers reported myalgia and cramps, 17 % experienced mild-to-moderate muscle weakness and 8 % experienced dilated cardiomyopathy, with a mean onset age of approximately 30 years. Another study found that echocardiographic examination was abnormal in up to 38% of DMD female carriers - some with dilated cardiomyopathy, and some with left ventricle dilatation.
Overall, however significance of carrying a single mutation of recessive myopathy is widely unexplored. No study has yet investigated the characteristics of single mutation carriers of recessive myopathy in an observational, cross-sectional study.
Aim:
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Verified carrier status of recessive myopathy mutation before entry into the study
- •Age of 18 years or older
排除标准
- •Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
- •Claustrophobia
- •Pregnancy at the time of MRI
- •After investigators judgement
- •Healthy controls:
- •Inclusion Criteria:
- •Age of 18 years or older
- •Exclusion Criteria:
- •Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
- •Claustrophobia
- •Pregnancy at the time of MRI
- •After investigators judgement
结局指标
主要结局
Cardiac status
时间窗: MRI of cardiac status and muscles takes around 1,5 hours
We will use MRI with a contrast agent (gadolinium). Kidney function and contrast allergy status will be tested prior to use of contrast agent, and avoided if the participant is not suitable for contrast injection.
Muscle tissue quality
时间窗: MRI of cardiac status and muscles takes around 1,5 hours
Muscle tissue cross sectional area and fat percent will be investigated and measured by Dixon MRI scan.
次要结局
- Muscle strength(Testing takes around 10-20 minutes)
- ECG(Estimated time: 5 minutes.)
- Holter monitor(A Holter monitor device will be attached on test day 1, and worn until test day 2 (24-48 hours))
- Serum CK-levels(Estimated time 5 minutes.)
研究者
Tove Freja Maria Fornander
Student researcher
Rigshospitalet, Denmark