title: Autosomal recessive cerebellar ataxia type 3 due to ANO10 mutations: delineation and genotype-phenotype correlation study.
abstract: OBJECTIVE
  ANO10 mutations have been reported to cause a novel form of autosomal recessive cerebellar ataxia (ARCA). Our objective was to report 9 ataxic patients carrying 8 novel ANO10 mutations to improve the delineation of this form of ARCA and provide genotype-phenotype correlation.
  
  
  METHODS
  The ANO10 gene has been sequenced in 186 consecutive patients with ARCA. The detailed phenotype of patients with ANO10 mutations was investigated and compared with the 12 previously reported cases. The mean age at onset was 33 years (range, 17-43 years), and the disease progression was slow. Corticospinal tract signs were frequent, including extensor plantar reflexes and/or diffuse tendon reflexes and/or spasticity. No patient in our series had peripheral neuropathy. Magnetic resonance imaging of the brains of our patients revealed marked cerebellar atrophy. The most frequent mutation, a mononucleotide expansion from a polyA repeat tract (c.132dupA) that causes protein truncation, was never observed in homozygosity. Only 2 truncating mutations were reported in homozygosity, one of which (c.1150-1151del) was associated with juvenile or adolescent onset and mental retardation, whereas we show that the presence of at least 1 missense or in-frame mutation is associated with adult onset and slow progression.
  
  
  CONCLUSIONS
  An ANO10 mutation is responsible for ARCA that is mainly characterized by cerebellar atrophy and lack of peripheral neuropathy. We therefore suggest naming this entity autosomal recessive cerebellar ataxia type 3 (ARCA3).
authors.affiliation: Département de neurologie, hôpitaux universitaires de Strasbourg, hôpital de Hautepierre, Strasbourg, France2Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la R.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Renaud
authors.affiliation: Département de neurologie, hôpitaux universitaires de Strasbourg, hôpital de Hautepierre, Strasbourg, France2Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la R.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Anheim
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Erik-Jan
authors.initials: EJ
authors.lastname: Kamsteeg
authors.affiliation: Département de neurologie, hôpitaux universitaires de Strasbourg, hôpital de Hautepierre, Strasbourg, France2Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la R.
authors.forename: Martial
authors.initials: M
authors.lastname: Mallaret
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de recherche de l'institut du cerveau et de la moelle épinière, Paris, France6AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Mochel
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Sascha
authors.initials: S
authors.lastname: Vermeer
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Strasbourg, Strasbourg, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Drouot
authors.affiliation: Département de neurologie, hôpitaux universitaires de Marseille, hôpital de la Timone, Marseille, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Pouget
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Strasbourg, Strasbourg, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Redin
authors.affiliation: Département de neurologie, hôpitaux universitaires de Marseille, hôpital de la Timone, Marseille, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Salort-Campana
authors.affiliation: Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
authors.forename: Hubertus P H
authors.initials: HP
authors.lastname: Kremer
authors.affiliation: Department of Neurology, Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, the Netherlands.
authors.forename: Corien C
authors.initials: CC
authors.lastname: Verschuuren-Bemelmans
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Strasbourg, Strasbourg, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Muller
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Scheffer
authors.affiliation: Université Pierre et Marie Curie Paris 6, Centre de recherche de l'institut du cerveau et de la moelle épinière, Paris, France6AP-HP, Hôpital de la Salpêtrière, Département de Génétique et Cytogénétique, Paris, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Durr
authors.affiliation: Département de neurologie, hôpitaux universitaires de Strasbourg, hôpital de Hautepierre, Strasbourg, France2Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la R.
authors.forename: Christine
authors.initials: C
authors.lastname: Tranchant
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université de Strasbourg, Strasbourg, France9Laboratoire de Génétique des Maladies Rar.
authors.forename: Michel
authors.initials: M
authors.lastname: Koenig
mesh_terms: D000293:Adolescent; D000328:Adult; D000075368:Anoctamins; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D013132:Spinocerebellar Degenerations / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D055815:Young Adult; D020754:Spinocerebellar Ataxias
chemical_list: C000594870:ANO10 protein, human; D000075368:Anoctamins; D008565:Membrane Proteins