Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype
Neurofilament light chain polypeptide gene mutations in Charcot-Marie-Tooth disease: nonsense mutation probably causes a recessive phenotype
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DOI：
10.1038/jhg.2008.13
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发表时间：
2009-02-01
影响因子：
3.5
通讯作者：
Hayasaka, Kiyoshi
中科院分区：
文献类型：
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作者：
Abe, Akiko;Numakura, Chikahiko;Hayasaka, Kiyoshi
神经丝轻链多肽（NEFL）形成神经元和轴突中的主要中间丝。NEFL突变是显性腓骨肌萎缩症（CMT）轴突或脱髓鞘形式的原因。我们研究了223例日本CMT患者的NEFL，这些患者在脱髓鞘形式中对PMP 22、MPZ、GJB 1、LITAF、EGFR 2、GDAP 1、MTMR 2和PRX呈阴性，在轴突形式中对MFN 2、MPZ、GJB 1、HSP 27、HSP 22和加尔斯呈阴性。我们在5名无关患者中检测到4种杂合错义突变-Pro 8Leu、Glu 90 Lys、Asn 98 Ser和Glu 396 Lys，在另1名患者中检测到纯合无义突变Glu 140 Stop。所有患者都有轻度至中度的神经传导速度延迟，可能是由于大直径纤维的损失造成的。这是NEFL纯合无义突变的首次报道。我们的研究结果表明，无义NEFL突变可能导致隐性表型，而错义突变，导致显性表型。
The neurofilament light chain polypeptide (NEFL) forms the major intermediate filament in neurons and axons. NEFL mutation is a cause of axonal or demyelinating forms of dominant Charcot-Marie-Tooth disease (CMT). We investigated NEFL in 223 Japanese CMT patients who were negative for PMP22, MPZ, GJB1, LITAF, EGR2, GDAP1, MTMR2 and PRX in the demyelinating form and negative for MFN2, MPZ, GJB1, HSP27, HSP22 and GARS in the axonal form. We detected four heterozygous missense mutations-Pro8Leu, Glu90Lys, Asn98Ser and Glu396Lys-in five unrelated patients and a homozygous nonsense mutation, Glu140Stop, in one other patient. All patients had mildly to moderately delayed nerve conduction velocities, possibly caused by a loss of large diameter fibers. This is the first report of a homozygous nonsense mutation of NEFL. Results of our study show that nonsense NEFL mutations probably cause a recessive phenotype, in contrast to missense mutations, which cause a dominant phenotype.