腓骨肌萎缩症2型一个家系的临床和病理及分子遗传学研究

Clinical,pathological and genetic studies in a Chinese Charcot-MarieTooth disease type 2 family

目的:报道一个腓骨肌萎缩症2型(CM T 2)大家系。方法:对家系中所有成员进行详细的体格检查,6名患者进行肌电图和神经传导速度检查,先证者进行腓肠神经活检,采用高度多态性短串联重复(STR)法检测PM P 22基因大片段重复突变,对PM P 22、M PZ和NEFL基因编码区致病突变,采用聚合酶链式反应-单链构象多态(PCR-SSCP)技术结合DNA测序进行检测。最后对该家系进行全基因组扫描。结果:除了2名患者同时有下肢近端和远端肌肉萎缩和无力外,所有患者都表现为不同程度的以下肢为重的肢体远端肌肉萎缩和无力,轻到中度的感觉障碍。6名患者正中神经运动神经传导速度都正常,肌电图检查均可见巨大运动单元电位、纤颤电位和正锐波,腓肠神经活检证实为轴突型周围神经病。STR法未检测到PM P 22基因大片段重复突变,PCR-SSCP技术未检测到PM P 22、M PZ和NEFL基因编码区致病突变。全基因组扫描最终将其疾病基因定位在12q24.2-q24.3。结论:检查结果符合CM T 2型的诊断,该家系是一种罕见的CM T 2亚型。

Objective： To report a Chinese Charcot-Marie-Tooth disease type 2 （CMT2） family. Methods： All the members in the family were studied clinically,and 6 patients were studied electrophysiologically. Sural nerve biopsy was performed in the proband. PMP22 gene duplications were detected by highly polymorphic short tandem repeat. Point mutation analysis of PMP22,MPZ and NEFL gene was screened by PCR-SSCP combined with DNA direct sequencing. A genome-wide screening was carried out to the family. Results ： Except 2 who had weakness and atrophy in both proximal and distal muscles of the lower limbs, all patients presented muscle wasting and a predominating weakness of distal parts of the lower limbs,and mild to moderate sensory impairments. In 6 patients who were subjected to elctrophysiological examinations,median-nerve conduction velocity （NCV） of the median nerve was normal. Electromyograms （EMGs） revealed signs of denervation with large motor unit potentials, fibrillation potentials and positive sharp waves. Sural nerve biopsy of the proband confirmed the presence of axonal neuropathy with an important loss of large myelinating fibers and a large number of clusters with mostly thinly myelinated axons. PMP22,MPZ and NEFL gene mutations were not found. The results of genome-wide screening revealed a linkage of CMT2 to a locus at chromosome 12q24. Conclusion： The results are consistent with the diagnosis of CMT2. This family represents a rare genetic type of CMT2 which can be designated as CMT2L.