IMR Press / JIN / Volume 19 / Issue 1 / DOI: 10.31083/j.jin.2020.01.1239
Open Access Case Report
Late-onset autosomal recessive cerebellar ataxia and neuropathy with a novel splicing mutation in the ATM gene
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1 Division of Neurology, Department of Internal Medicine, Jichi Medical University School of Medicine, Tochigi, 329-0498, Japan
2 Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto, 606-8501, Japan
3 Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, 183-0042, Japan
*Correspondence: (Haruo Shimazaki)
: Deceased July 16, 2014
J. Integr. Neurosci. 2020, 19(1), 125–129;
Submitted: 19 November 2019 | Accepted: 24 February 2020 | Published: 30 March 2020
Copyright: © 2020 Shimazaki et al. Published by IMR press.
This is an open access article under the CC BY-NC 4.0 license (

Autosomal recessive cerebellar ataxias comprise many types of diseases. The most frequent autosomal recessive cerebellar ataxias are Friedreich ataxia, but other types are relatively rare. We encountered a consanguineous family with two cases of late-onset cerebellar ataxia with neuropathy. We performed whole-exome sequencing in one patient and confirmed by Sanger sequencing in other family members. Neurological examination revealed cerebellar ataxia, hand tremor, and neck dystonia, distal muscle wasting, and diminished tendon reflexes. The patients had no conjunctival telangiectasia or immunodeficiency. Blood examination revealed slightly elevated α-fetoprotein. Brain MRI demonstrated marked cerebellar atrophy and mild brainstem atrophy. The electrophysiologic study and nerve biopsy showed axonal neuropathy. Whole-exome sequencing revealed a novel homozygous missense variant (NM_000051.3: c.496G > C) in the ataxia-telangiectasia mutated gene. This homozygous variant was found in another patient, co-segregated within the family members—this variant results in aberrant splicing (skipping exon 5) on RT-PCR analysis. We identified the ataxia-telangiectasia mutated variant in an adult, late-onset autosomal recessive cerebellar ataxias family. We should consider ataxia-telangiectasia even in late-onset autosomal recessive cerebellar ataxias without telangiectasia or immunodeficiency.

Autosomal recessive cerebellar ataxia
muscle atrophy
ataxia-telangiectasia mutated
splicing mutation
whole-exome sequencing
Figure 1.
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