T118M PMP22突变导致功能部分丧失和遗传性压迫易感性神经病样神经病变。
T118M PMP22 mutation causes partial loss of function and HNPP-like neuropathy.
作者信息
Shy Michael E, Scavina Mena T, Clark Alisa, Krajewski Karen M, Li Jun, Kamholz John, Kolodny Edwin, Szigeti Kinga, Fischer Richard A, Saifi Gulam Mustafa, Scherer Steven S, Lupski James R
机构信息
Department of Neurology and Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI 48201, USA.
出版信息
Ann Neurol. 2006 Feb;59(2):358-64. doi: 10.1002/ana.20777.
OBJECTIVE
To determine the clinical consequences of the PMP22 point mutation, T118M, which has been previously considered to either cause an autosomal recessive form of Charcot-Marie-Tooth (CMT) disease or be a benign polymorphism.
METHODS
We analyzed patients from five separate kindreds and characterized their peripheral nerve function by clinical and electrophysiological methods.
RESULTS
All heterozygous patients had clinical and/or electrophysiological features of a neuropathy similar to hereditary neuropathy with liability to pressure palsies (HNPPs). The homozygous patient had a severe axonal neuropathy without features of demyelination.
INTERPRETATION
These findings suggest that T118M PMP22 retains some normal PMP22 activity, allowing the formation of compact myelin and normal nerve conduction velocities in the homozygous state. Taken together, these findings suggest that T118M is a pathogenic mutation causing a dominantly inherited form of CMT by a partial loss of PMP22 function.
目的
确定PMP22点突变T118M的临床后果，该突变此前被认为要么导致常染色体隐性遗传性腓骨肌萎缩症（CMT），要么是一种良性多态性。
方法
我们分析了来自五个不同家族的患者，并通过临床和电生理方法对他们的周围神经功能进行了表征。
结果
所有杂合子患者都具有与遗传性压力易感性神经病（HNPP）相似的神经病临床和/或电生理特征。纯合子患者患有严重的轴索性神经病，无脱髓鞘特征。
解读
这些发现表明，T118M PMP22保留了一些正常的PMP22活性，使得在纯合状态下能够形成致密髓鞘并具有正常的神经传导速度。综上所述，这些发现表明T118M是一种致病突变，通过PMP22功能的部分丧失导致显性遗传形式的CMT。
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