Motley William W, Palaima Paulius, Yum Sabrina W, Gonzalez Michael A, Tao Feifei, Wanschitz Julia V, Strickland Alleene V, Löscher Wolfgang N, De Vriendt Els, Koppi Stefan, Medne Livija, Janecke Andreas R, Jordanova Albena, Zuchner Stephan, Scherer Steven S
Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA Department of Medicine, Pennsylvania Hospital, University of Pennsylvania, Philadelphia, Pennsylvania 19107, USA.
Molecular Neurogenomics Group, VIB Department of Molecular Genetics, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium Laboratory of Neurogenetics, Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, 2650-Antwerpen, Belgium.
Brain. 2016 Jun;139(Pt 6):1649-56. doi: 10.1093/brain/aww055. Epub 2016 Mar 23.
We performed whole exome sequencing on a patient with Charcot-Marie-Tooth disease type 1 and identified a de novo mutation in PMP2, the gene that encodes the myelin P2 protein. This mutation (p.Ile52Thr) was passed from the proband to his one affected son, and segregates with clinical and electrophysiological evidence of demyelinating neuropathy. We then screened a cohort of 136 European probands with uncharacterized genetic cause of Charcot-Marie-Tooth disease and identified another family with Charcot-Marie-Tooth disease type 1 that has a mutation affecting an adjacent amino acid (p.Thr51Pro), which segregates with disease. Our genetic and clinical findings in these kindred demonstrate that dominant PMP2 mutations cause Charcot-Marie-Tooth disease type 1.
我们对一名1型遗传性运动感觉神经病患者进行了全外显子组测序，并在编码髓磷脂P2蛋白的基因PMP2中鉴定出一个新生突变。该突变（p.Ile52Thr）从先证者遗传至其一名患病儿子，并与脱髓鞘性周围神经病的临床和电生理证据共分离。然后，我们对136名病因不明的欧洲遗传性运动感觉神经病先证者进行了筛查，发现另一个1型遗传性运动感觉神经病家族，该家族存在一个影响相邻氨基酸的突变（p.Thr51Pro），且该突变与疾病共分离。我们在这些家族中的遗传学和临床研究结果表明，显性PMP2突变可导致1型遗传性运动感觉神经病。
