Objective: To investigate the Cx32 mutation features and the clinical manifestations of Chinese patients with Charcot-Marie-Tooth disease(CMT). Methods: Twenty-four of 65 unrelated CMT patients were selected for Cx32 mutation screening after the exclusion of the CMT1A 1.5 Mb duplication and male-to-male transmission. The motor and sensory nerve conduction studies were performed in all probands and most of their affected family members to establish the clinical CMT1 ,CMT2 or CMT intermediate diagnosis. The presence of mutations in the coding region of Cx32 was detected by single-strand conformation polymorphism analysis combined with direct sequencing. Results: We found 7 different point mutations in the coding region of Cx32 in a total of 7 families. All the patients were mildly to moderately affected with a clinical CMT1 or CMT intermediate diagnosis. The mutation Arg15Gln was inherited with X-linked recessive trait in family 1 involved in our study. The Arg75Trp mutation was detected in a family with X-linked dominant CMT and autosomal recessive nonsydromic hearing loss. The clinical phenotype of the Thr188Ala mutation was firstly reported. Conclusion: Seven different Cx32 point mutations were detected and the percentage of Chinese CMT families with Cx32 mutation is about 10% in our study. The inheritance model of CMT secondary to Cx32 mutation could be X-linked dominant, X-linked recessive or sporadic. Male patients are usually more severely affected than females with slower nerve conduction velocities. Cx32 mutation screening should be firstly performed in those CMT families without male-to-male transmission and CMT1A duplication.
目的研究经基因诊断确诊的遗传性压迫易感性神经病(hereditary neuropathy with liability to pressure palsies,HNPP)患者的临床特点和电生理特征。方法对来自4个家系的5例HNPP患者进行基因诊断,并总结患者的临床特点,同时分析其电生理特征,包括肌电图(EMG)、运动神经传导速度(MCV)和感觉神经传导速度(SCV)。结果5例患者均存在周围髓鞘蛋白22 (peripheral myelination protein 22,PMP22)基因缺失。HNPP临床主要表现为反复发作的肢体麻木、无力,神经传导存在广泛异常。结论电生理检查对HNPP的诊断很重要,基因检测发现PMP22基因缺失是诊断HNPP的金标准。
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。
