Genetic heterogeneity of motor neuropathies
Open Access
- 28 March 2017
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 88 (13), 1226-1234
- https://doi.org/10.1212/wnl.0000000000003772
Abstract
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.Keywords
This publication has 43 references indexed in Scilit:
- FastUniq: A Fast De Novo Duplicates Removal Tool for Paired Short ReadsPLOS ONE, 2012
- Discoidin Domain Receptors Promote α1β1- and α2β1-Integrin Mediated Cell Adhesion to Collagen by Enhancing Integrin ActivationPLOS ONE, 2012
- Defective Presynaptic Choline Transport Underlies Hereditary Motor NeuropathyAmerican Journal of Human Genetics, 2012
- Genetic disruption of Pten in a novel mouse model of tomaculous neuropathyEMBO Molecular Medicine, 2012
- Phenotypic Variability in a Large Czech Family with a Dynamin 2–Associated Charcot-Marie-Tooth NeuropathyJournal of Neurogenetics, 2011
- Charcot–Marie–Tooth disease in Northern England: Figure 1Journal of Neurology, Neurosurgery & Psychiatry, 2011
- A novel STAT5B mutation causing GH insensitivity syndrome associated with hyperprolactinemia and immune dysfunction in two male siblingsActa Endocrinologica, 2010
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Deleterious Variants of FIG4, a Phosphoinositide Phosphatase, in Patients with ALSAmerican Journal of Human Genetics, 2009
- Molecular genetics of distal hereditary motor neuropathiesHuman Molecular Genetics, 2004