Miltenberger-Miltenyi Gabriel, Janecke Andreas R, Wanschitz Julia V, Timmerman Vincent, Windpassinger Christian, Auer-Grumbach Michaela, Löscher Wolfgang N
Section of Clinical Genetics, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria.
Arch Neurol. 2007 Jul;64(7):966-70. doi: 10.1001/archneur.64.7.966.
To date, 13 different neurofilament light-chain polypeptide gene (NEFL) mutations have been identified in 55 patients with Charcot-Marie-Tooth disease (CMT) from 16 families. NEFL mutations were found to be associated with axonal and demyelinating variants of CMT.
To describe the clinical features of 11 patients with CMT and NEFL mutations and to explore possible genotype-phenotype correlations.
Standardized neuromuscular and nerve conduction studies were performed, and the coding regions of the peripheral myelin protein 22 (PMP22), myelin protein zero (MPZ), gap junction beta-1 protein (GJB1), and NEFL genes were analyzed by direct DNA sequencing.
Two university hospitals in Austria (referral centers for neuromuscular disorders). Patients Eleven patients with CMT and NEFL mutations. Main Outcome Measure We genotyped NEFL in all of the patients and healthy relatives and correlated the genotype with the phenotype.
A novel NEFL mutation (p.L93P) was detected in 1 family with 4 affected individuals exhibiting a severe CMT phenotype. Nerve conduction velocities were intermediately slowed to a range of 35 to 39 m/s. In a second family and in a sporadic patient, a p.P8R mutation was identified with intermediate and severe nerve conduction slowing.
The results argue against an obvious genotype-phenotype correlation regarding disease onset, degree of muscle weakness, and nerve conduction slowing caused by NEFL mutations.
迄今为止，在来自16个家庭的55例夏科-马里-图斯病（CMT）患者中已鉴定出13种不同的神经丝轻链多肽基因（NEFL）突变。发现NEFL突变与CMT的轴索性和脱髓鞘性变异相关。
描述11例患有CMT和NEFL突变患者的临床特征，并探索可能的基因型-表型相关性。
进行标准化的神经肌肉和神经传导研究，并通过直接DNA测序分析外周髓鞘蛋白22（PMP22）、髓鞘蛋白零（MPZ）、缝隙连接β-1蛋白（GJB1）和NEFL基因的编码区。
奥地利的两家大学医院（神经肌肉疾病转诊中心）。患者11例患有CMT和NEFL突变的患者。主要观察指标我们对所有患者及其健康亲属进行NEFL基因分型，并将基因型与表型相关联。
在一个有4名受累个体的家庭中检测到一种新的NEFL突变（p.L93P），这些个体表现出严重的CMT表型。神经传导速度中度减慢，范围为35至39米/秒。在另一个家庭和一名散发患者中，鉴定出p.P8R突变，伴有中度和重度神经传导减慢。
结果表明，关于NEFL突变引起的疾病发作、肌肉无力程度和神经传导减慢，不存在明显的基因型-表型相关性。
