PT -期刊文章AU - m . ZimońAU - j . Baets AU -通用Fabrizi AU - e . Jaakkola AU - d . Kabzińska AU - j .尿布垫盟A.B.辛德勒AU -湄Cornblath盟K.H. Fischbeck AU - m . Auer-Grumbach AU - c . Guelly AU - n Huber AU - e . De Vriendt盟诉Timmerman AU -美国苏特AU - i Hausmanowa-Petrusewicz盟- a Niemann AU - a . Kochański盟- p . De Jonghe AU - a Jordanova TI -主导< em > GDAP1 < / em >突变原因主要是轻度CMT - 10.1212 / WNL表型援助。0 b013e318228fc70 DP - 2011 8月09年TA -神经首页病学第六PG - 540 - 548 - 77 IP - 6 4099 - //www.ez-admanager.com/content/77/6/540.short 4100 - //www.ez-admanager.com/content/77/6/540.full所以Neurology2011 09年8月;77 AB -目的:Ganglioside-induced分化associated-protein 1 (GDAP1)突变通常与常染色体隐性(ARCMT)神经病变;腓骨肌萎缩然而,在罕见的情况下,他们也导致常染色体显性(ADCMT)腓骨肌萎缩。我们旨在调查致病频率的杂合的GDAP1 ADCMT及其相关的突变表型。方法:我们进行突变分析群体的ADCMT病人通过双向测序的编码区域和exon-intron GDAP1的边界。基因内使用一个等位基因量化分析GDAP1删除被排除在外。我们确认一个序列变异的病原特征通过体外实验分析线粒体形态和功能。结果:在8疾病(CMT)家庭我们确定腓骨肌萎缩4致病性杂合的GDAP1突变,3是小说。三个突变显示疾病外显率降低。疾病发病的影响个体变量,从幼儿到成年。 Disease progression was slow in most patients and overall severity milder than typically seen in autosomal recessive GDAP1 mutations. Electrophysiologic changes are heterogeneous but compatible with axonal neuropathy in the majority of patients. Conclusions: With this study, we broaden the phenotypic and genetic spectrum of autosomal dominant GDAP1-associated neuropathies. We show that patients with dominant GDAP1 mutations may display clear axonal CMT, but may also have only minimal clinical and electrophysiologic abnormalities. We demonstrate that cell-based functional assays can be reliably used to test the pathogenicity of unknown variants. We discuss the implications of phenotypic variability and the reduced penetrance of autosomal dominant GDAP1 mutations for CMT diagnostic testing and counseling. ADCMT=autosomal dominant Charcot-Marie-Tooth; ARCMT=autosomal recessive Charcot-Marie-Tooth; CMT=Charcot-Marie-Tooth; DQ=dosage quotient; GDAP1=ganglioside-induced differentiation-associated protein 1; MAQ=Multiplex Amplicon Quantification; NCV=nerve conduction velocity; PEG=polyethylene glycol; STR=short tandem repeat; VFP=vocal fold paresis

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