title: Absence of HINT1 mutations in a UK and Spanish cohort of patients with inherited neuropathies.
abstract: Biallelic mutations in the HINT1 gene were recently identified as the cause of axonal neuropathy with neuromyotonia. It has been suggested that HINT1 mutations may indeed account for 11% of all inherited neuropathies with autosomal recessive inheritance. However, 81% of patients HINT1-related neuropathies reported to date are originally from five European countries and the global prevalence of the disorder is still unknown. In our study, we aimed to determine the frequency of HINT1 mutations by direct sequencing in a cohort of 152 patients with inherited neuropathies from the UK and Spain, where no cases have been described to date. We failed to identify patients with clinical myotonia, neuromyotonia or pathogenic mutations in HINT1. Our results support that HINT1-related neuropathies are not homogeneously distributed among European populations, which may be explained by founder effects. This geographical variability also underlines the importance of considering the ethnic background when screening for mutations in neuropathy-related genes.
authors.affiliation: MRC Centre for Neuromuscular Diseases, National Hospital for Neurology and Neurosurgery and UCL Institute of Neurology, Box 108, Queen Square, London, WC1N 3BG, UK.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Horga
authors.forename: Ellen
authors.initials: E
authors.lastname: Cottenie
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Tomaselli
authors.forename: Ricard
authors.initials: R
authors.lastname: Rojas-García
authors.forename: Maria
authors.initials: M
authors.lastname: Salvado
authors.forename: Liliana
authors.initials: L
authors.lastname: Villarreal-Pérez
authors.forename: Josep
authors.initials: J
authors.lastname: Gamez
authors.forename: Celedonio
authors.initials: C
authors.lastname: Márquez-Infante
authors.forename: Henry
authors.initials: H
authors.lastname: Houlden
authors.forename: Mary M
authors.initials: MM
authors.lastname: Reilly
mesh_terms: D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D059645:Mutation Rate; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D013030:Spain; D006113:United Kingdom
chemical_list: C063306:HINT1 protein, human; D009419:Nerve Tissue Proteins