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Exome sequencing reveals a novel ANO10 mutation in a Japanese patient with autosomal recessive spinocerebellar ataxia
Author(s) -
Maruyama H.,
Morino H.,
Miyamoto R.,
Murakami N.,
Hamano T.,
Kawakami H.
Publication year - 2014
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.12140
Subject(s) - exome sequencing , genetics , spinocerebellar ataxia , mutation , biology , ataxia , exome , dna sequencing , gene , neuroscience
To the Editor : Spinocerebellar ataxia autosomal recessive type 10 (SCAR10, OMIM 613728) is caused by the mutation of ANO10 (1). The clinical phenotype was characterized by ataxia, hyper-reflexia, normal plantar reflex, downbeat nystagmus and lower motor neuron involvement. Here, we report a novel ANO10 mutation in a patient with autosomal recessive spinocerebellar ataxia (ARSCA), using exome sequencing. The research procedure was approved by the Ethics Committee of Hiroshima University. All of the examinations were performed after obtaining informed consent from the patient. Control exomes were obtained from patients undergoing exome analysis for diseases other than SCA. A Japanese patient with cerebellar ataxia born to consanguineous parents had a homozygous nonsense ANO10 (c.609C>G, p.Y203X) mutation. The identified mutation was validated with conventional Sanger sequencing. This mutation was not detected in our control exomes. A 58-year-old man had presented with loss of consciousness at age 42 and was treated with 800 mg of sodium valproate (further information could not be obtained). He had noticed a tendency to fall at age 46 and dysarthria at age 54. However, he continued to satisfactorily function at work. At age of 58, he presented with saccadic eye movement, hyper-reflexia, decreased vibration sense and constipation. Muscle atrophy, nystagmus and tortuosity of the conjunctival vessels were not observed. Electromyography was normal. His MiniMental State Examination score was 29. Brain magnetic resonance imaging (MRI) showed mild cerebellar atrophy, and brain stem was slightly atrophic at age 57 (Fig. 1). Single photon emission computed tomography showed a decrease in cerebellar flow. Previously reported SCAR10 cases have originated from the Netherlands, Serbia and France (1, 2), and this is the first case reported outside Europe. In contrast to our case, previous reported cases also presented muscle atrophy, nystagmus, tortuosity of the conjunctival vessels and intellectual deficit. In addition, in our case, decreased vibration sense and constipation were detected and the age of onset was relatively late. These characteristics should be considered when diagnosing SCAR10. Previously, homozygous missense mutation, homozygous frame-shift mutation and compound Fig. 1. Brain magnetic resonance imaging at age of 57: T1 sagittal image. Mild cerebellar atrophy was observed.