Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Mi Hyun Park, Hae Mi Woo, Young Bin Hong, Ji Hoon Park, Bo Ram Yoon, Jin Mo Park, Jeong Hyun Yoo, Heasoo Koo, Jong Hee Chae, Ki Wha Chung, Byung Ok Choi, Soo Kyung Koo

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9 Scopus citations


Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12-15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported.

Original languageEnglish
Pages (from-to)171-182
Number of pages12
Issue number3
StatePublished - Aug 2014

Bibliographical note

Funding Information:
This work was supported by the Korea National Institute of Health intramural research program 4800-4845-302-210-13 (2012-N61001-00) and 4800-4861-307-210-13 (2012-NG61004-00), the Basic Science Research Program through the National Research Foundation (NRF) funded by the Ministry of Education (2011-0021533), and the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (A120182).


  • C10orf2
  • Infantile-onset spinocerebellar ataxia (IOSCA)
  • Mitochondria
  • Myopathy
  • Neuropathy
  • Whole exome sequencing (WES)


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