Bourteel H, Vermersch P, Cuisset J-M, Maurage C-A, Laforet P, Richard P, Stojkovic T
Service de Neurologie inflammatoire et infectieuse, Hôpital Roger Salengro, CHRU Lille, France.
J Neurol Neurosurg Psychiatry. 2009 Dec;80(12):1405-8. doi: 10.1136/jnnp.2007.141804.
Limb-girdle muscular dystrophy 2I (LGMD2I) is caused by mutations in the fukutin-related protein gene FKRP, which is also involved in congenital muscular dystrophy (MDC1C).
To evaluate the clinical, biological, radiological and mutational characteristics of LGMD2I patients with FKRP mutation.
Eleven patients from nine families from the north of France were studied. Demographical data, muscular testing results, cardiac and respiratory examinations, muscle histological features and a genetic analysis of the FKRP gene for each patient are reported. Eight patients underwent brain MRI and seven neuropsychological tests.
The patients included six women and five men. The mean age at onset was 9 years (range 1.5 to 23 years). Five patients remained self-ambulatory, whereas the other six were confined to a wheelchair by a mean age of 19 years, after a mean disease duration of 10 years. Nine patients suffered from restrictive respiratory insufficiency, and two male patients had severe dilated cardiomyopathy. Neuropsychological tests revealed memory impairment in four cases. Brain MRI revealed cerebral abnormalities in four patients (4/8). Ten patients were carriers of the common L276I mutation, which was either homozygous (four patients) or heteroallelic with another mutation (six patients). Among the mutations found, three were novel: L322V, L489R and R275G.
This study reveals inter- and intrafamilial phenotypic variability in LGMD2I, with a preponderance of myocardiopathy and restrictive respiratory insufficiency. It also demonstrates central nervous involvement, probably associated with changes in alpha-dystroglycan expression in the brain.
肢带型肌营养不良2I型（LGMD2I）由福金蛋白相关蛋白基因FKRP突变引起，该基因也与先天性肌营养不良（MDC1C）有关。
评估FKRP基因突变的LGMD2I患者的临床、生物学、放射学和突变特征。
对来自法国北部9个家庭的11例患者进行了研究。报告了每位患者的人口统计学数据、肌肉测试结果、心脏和呼吸检查、肌肉组织学特征以及FKRP基因的遗传分析。8例患者接受了脑部MRI检查，7例接受了神经心理学测试。
患者包括6名女性和5名男性。平均发病年龄为9岁（范围1.5至23岁）。5例患者仍可自主行走，而其他6例患者在平均病程10年后，平均19岁时需依靠轮椅行动。9例患者患有限制性呼吸功能不全，2例男性患者患有严重的扩张型心肌病。神经心理学测试显示4例患者存在记忆障碍。脑部MRI显示4例患者（4/8）存在脑部异常。10例患者携带常见的L276I突变，其中4例为纯合突变，6例为与另一种突变的杂合等位基因。在所发现的突变中，有3种是新的：L322V、L489R和R275G。
本研究揭示了LGMD2I患者家庭间和家庭内的表型变异性，以心肌病和限制性呼吸功能不全为主。它还证明了中枢神经系统受累，可能与大脑中α-肌营养不良蛋白聚糖表达的变化有关。
