Genetic heterogeneity of motor neuropathies

被引：96

作者：

Bansagi, Boglarka ^{[1
,2
]}

Griffin, Helen ^{[1
,2
]}

Whittaker, Roger G. ^{[3
]}

Antoniadi, Thalia ^{[4
]}

Evangelista, Teresinha ^{[1
,2
]}

Miller, James ^{[3
]}

Greenslade, Mark ^{[4
]}

Forester, Natalie ^{[4
]}

Duff, Jennifer ^{[1
,2
]}

Bradshaw, Anna ^{[1
,2
]}

Kleinle, Stephanie ^{[5
]}

Boczonadi, Veronika ^{[1
,2
]}

Steele, Hannah ^{[1
,2
]}

Ramesh, Venkateswaran ^{[6
]}

Franko, Edit ^{[1
,2
,7
]}

Pyle, Angela ^{[1
,2
]}

Lochmueller, Hanns ^{[1
,2
]}

Chinnery, Patrick F. ^{[1
,2
,8
]}

Horvath, Rita ^{[1
,2
]}

机构：

[1] Newcastle Univ, Ctr Neuromuscular Dis, MRC, Newcastle Upon Tyne, Tyne & Wear, England

[2] Newcastle Univ, John Walton Muscular Dystrophy Res Ctr, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England

[3] Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne, Tyne & Wear, England

[4] North Bristol NHS Trust, Bristol Genet Lab, Pathol Sci, Southmead Hosp, Bristol, Avon, England

[5] Ctr Med Genet, Munich, Germany

[6] Newcastle Upon Tyne Fdn Hosp NHS Trust, Dept Paediat Neurol, Royal Victoria Infirm, Newcastle Upon Tyne, Tyne & Wear, England

[7] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford OX1 2JD, England

[8] Univ Cambridge, Dept Clin Neurosci, Cambridge Biomed Campus, Cambridge CB2 1TN, England

来源：

NEUROLOGY | 2017年 / 88卷 / 13期

基金：

欧洲研究理事会; 英国惠康基金; 英国医学研究理事会;

关键词：

MARIE-TOOTH DISEASE; PHENOTYPIC VARIABILITY; MUTATIONS CAUSE; PREVALENCE; SPECTRUM;

D O I：

10.1212/WNL.0000000000003772

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Objective: To study the prevalence, molecular cause, and clinical presentation of hereditary motor neuropathies in a large cohort of patients from the North of England. Methods: Detailed neurologic and electrophysiologic assessments and next-generation panel testing or whole exome sequencing were performed in 105 patients with clinical symptoms of distal hereditary motor neuropathy (dHMN, 64 patients), axonal motor neuropathy (motor Charcot-Marie-Tooth disease [CMT2], 16 patients), or complex neurologic disease predominantly affecting the motor nerves (hereditary motor neuropathy plus, 25 patients). Results: The prevalence of dHMN is 2.14 affected individuals per 100,000 inhabitants (95% confidence interval 1.62-2.66) in the North of England. Causative mutations were identified in 26 out of 73 index patients (35.6%). The diagnostic rate in the dHMN subgroup was 32.5%, which is higher than previously reported (20%). We detected a significant defect of neuromuscular transmission in 7 cases and identified potentially causative mutations in 4 patients with multifocal demyelinating motor neuropathy. Conclusions: Many of the genes were shared between dHMN and motor CMT2, indicating identical disease mechanisms; therefore, we suggest changing the classification and including dHMN also as a subcategory of Charcot-Marie-Tooth disease. Abnormal neuromuscular transmission in some genetic forms provides a treatable target to develop therapies.

引用

页码：1226 / 1234

页数：9

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