title: ANO10 mutations cause ataxia and coenzyme Q₁₀ deficiency.
abstract: Inherited ataxias are heterogeneous disorders affecting both children and adults, with over 40 different causative genes, making molecular genetic diagnosis challenging. Although recent advances in next-generation sequencing have significantly improved mutation detection, few treatments exist for patients with inherited ataxia. In two patients with adult-onset cerebellar ataxia and coenzyme Q10 (CoQ10) deficiency in muscle, whole exome sequencing revealed mutations in ANO10, which encodes anoctamin 10, a member of a family of putative calcium-activated chloride channels, and the causative gene for autosomal recessive spinocerebellar ataxia-10 (SCAR10). Both patients presented with slowly progressive ataxia and dysarthria leading to severe disability in the sixth decade. Epilepsy and learning difficulties were also present in one patient, while retinal degeneration and cataract were present in the other. The detection of mutations in ANO10 in our patients indicate that ANO10 defects cause secondary low CoQ10 and SCAR10 patients may benefit from CoQ10 supplementation.
authors.affiliation: Department of Neurology, Columbia University Medical Center, New York, NY, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Balreira
authors.forename: Veronika
authors.initials: V
authors.lastname: Boczonadi
authors.forename: Emanuele
authors.initials: E
authors.lastname: Barca
authors.forename: Angela
authors.initials: A
authors.lastname: Pyle
authors.forename: Boglarka
authors.initials: B
authors.lastname: Bansagi
authors.forename: Marie
authors.initials: M
authors.lastname: Appleton
authors.forename: Claire
authors.initials: C
authors.lastname: Graham
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.forename: Vedrana Milic
authors.initials: VM
authors.lastname: Rasic
authors.forename: Hanns
authors.initials: H
authors.lastname: Lochmüller
authors.forename: Helen
authors.initials: H
authors.lastname: Griffin
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Ali
authors.initials: A
authors.lastname: Naini
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: Michio
authors.initials: M
authors.lastname: Hirano
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Quinzii
authors.forename: Rita
authors.initials: R
authors.lastname: Horvath
mesh_terms: D000293:Adolescent; D000328:Adult; D000075368:Anoctamins; D001259:Ataxia / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics*; D018908:Muscle Weakness / Q000175:diagnosis* / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D014451:Ubiquinone / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
chemical_list: C000594870:ANO10 protein, human; D000075368:Anoctamins; D008565:Membrane Proteins; D014451:Ubiquinone