Genetic heterogeneity of motor neuropathies
Boglarka Bansagi1, Helen Griffin1, Roger G Whittaker1
1From the MRC Centre for Neuromuscular Diseases and John Walton Muscular Dystrophy Research Centre, Institute of Genetic Medicine (B.B., H.G., T.E., J.D., A.B., V.B., H.S., E.F., A.P., H.L., P.F.C., R.H.), and Institute of Neuroscience (R.G.W., J.M.), Newcastle University, Newcastle upon Tyne; Bristol Genetics Laboratory (T.A., M.G., N.F.), Pathology Sciences, North Bristol NHS Trust, Southmead Hospital; Medical Genetic Center (S.K.), Munich, Germany; Department of Paediatric Neurology (V.R.), Royal Victoria Infirmary, Newcastle upon Tyne Foundation Hospitals NHS Trust; Nuffield Department of Clinical Neurosciences (E.F.), University of Oxford; and Department of Clinical Neurosciences (P.F.C.), Cambridge Biomedical Campus, University of Cambridge, UK.
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.
Related Concept Videos
01:27Principles of Pharmacogenetics: Types of Genetic Variants
01:24Local Anesthetics: Differential Sensitivity of Nerve Fibers
01:13Motor Units
Motor units come in different sizes, with smaller units...
00:46Motor Units
01:25Genetic Variation
Genes exist in different versions called alleles,...
02:59Animal Mitochondrial Genetics