title: Axonal neuropathy with neuromyotonia: there is a HINT.
abstract: Recessive mutations in the gene encoding the histidine triad nucleotide binding protein 1 (HINT1) were recently shown to cause a motor-predominant Charcot-Marie-Tooth neuropathy. About 80% of the patients exhibit neuromyotonia, a striking clinical and electrophysiological hallmark that can help to distinguish this disease and to guide diagnostic screening. HINT1 neuropathy has worldwide distribution and is particularly prevalent in populations inhabiting central and south-eastern Europe. With 12 different mutations identified in more than 60 families, it ranks among the most common subtypes of axonal Charcot-Marie-Tooth neuropathy. This article provides an overview of the present knowledge on HINT1 neuropathy with the aim to increase awareness and spur interest among clinicians and researchers in the field. We propose diagnostic guidelines to recognize and differentiate this entity and suggest treatment strategies to manage common symptoms. As a recent player in the field of hereditary neuropathies, the role of HINT1 in peripheral nerves is unknown and the underlying disease mechanisms are unexplored. We provide a comprehensive overview of the structural and functional characteristics of the HINT1 protein that may guide further studies into the molecular aetiology and treatment strategies of this peculiar Charcot-Marie-Tooth subtype.
authors.affiliation: Molecular Neurogenomics Group, Department of Molecular Genetics, VIB and University of Antwerp, Antwerpen 2610, Belgium.
authors.forename: Kristien
authors.initials: K
authors.lastname: Peeters
authors.affiliation: Department of Neurology, Medical University-Sofia, Sofia 1431, Bulgaria.
authors.forename: Teodora
authors.initials: T
authors.lastname: Chamova
authors.affiliation: Department of Neurology, Medical University-Sofia, Sofia 1431, Bulgaria.|Department of Cognitive Science and Psychology, New Bulgarian University, Sofia 1618, Bulgaria.
authors.forename: Ivailo
authors.initials: I
authors.lastname: Tournev
authors.affiliation: Molecular Neurogenomics Group, Department of Molecular Genetics, VIB and University of Antwerp, Antwerpen 2610, Belgium.|Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia 1431, Bulgaria.
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
mesh_terms: D002607:Charcot-Marie-Tooth Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015417:Hereditary Sensory and Motor Neuropathy / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D020386:Isaacs Syndrome / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009222:Myotonia / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010523:Peripheral Nervous System Diseases / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: C063306:HINT1 protein, human; D009419:Nerve Tissue Proteins
keywords: CMT; HINT1; clinical characteristics; neuromyotonia; neuropathy