A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: A clinical, pathological and genetic report

Yamamoto-Watanabe, Yukiko; Watanabe, Mitsunori; Okamoto, Koichi; Fujita, Yukio; Jackson, Mandy; Ikeda, Masaki; Nakazato, Yoichi; Ikeda, Yoshio; Matsubara, Etsuro; Kawarabayashi, Takeshi; Shoji, Mikio

doi:10.1016/j.jns.2010.06.008

« Previous Next »Journal of the Neurological Sciences
Volume 296, Issue 1 , Pages 59-63, 15 September 2010

A Japanese ALS6 family with mutation R521C in the FUS/TLS gene: A clinical, pathological and genetic report☆

Yukiko Yamamoto-Watanabe
- Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
Mitsunori Watanabe
- Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
- Corresponding author. Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan. Tel.: +81 172 39 5142; fax: +81 172 39 5143.
Koichi Okamoto
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
Yukio Fujita
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
Mandy Jackson
- Centre of Integrative Physiology, University of Edinburgh, Summerhall, Edinburgh, UK
Masaki Ikeda
- Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
Yoichi Nakazato
- Department of Human Pathology, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan
Yoshio Ikeda
- Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama 700-8558, Japan
Etsuro Matsubara
- Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
Takeshi Kawarabayashi
- Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan
Mikio Shoji
- Department of Neurology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562, Japan

Received 10 February 2010; received in revised form 28 May 2010; accepted 7 June 2010. published online 12 July 2010.

Abstract

Here we report a Japanese family with amyotrophic lateral sclerosis (ALS) characterized by very rapid progression, high penetrance and an autosomal dominant mode of inheritance. The phenotype includes atrophy of sternocleidomastoideus muscles, bulbar involvement, weakness of neck muscles and proximal muscle atrophy. These clinical symptoms are reminiscent of myopathy. All patients examined had similar clinical symptoms, age at onset and disease duration. The proband was found to have mutation R521C in the FUS/TLS gene, and was diagnosed as having ALS6. Autopsy material was available from the mother of the proband and FUS-immunoreactive neuronal and glial cytoplasmic inclusions were observed in the anterior horn of the spinal cord. While atrophy and weakness of the sternocleidomastoideus muscle is not emphasized in previous reports, this symptom may be a clinical hallmark of ALS6.

Abbreviations: SOD1, Cu/Zn superoxide dismutase, ALS, amyotrophic lateral sclerosis

Keywords: ALS6, Familial amyotrophic lateral sclerosis, FUS/TLS, Phenotype, Proximal muscle atrophy, Sternocleidomastoideus