Genotype–phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan
Tetsuya Akiyama MD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorHitoshi Warita MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorMasaaki Kato MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorAyumi Nishiyama MD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorRumiko Izumi MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorChikako Ikeda MD
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Search for more papers by this authorMasaki Kamada MD, PhD
Department of Neurological Intractable Disease Research, Kagawa University Faculty of Medicine, Kagawa, Japan
Search for more papers by this authorNaoki Suzuki MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorCorresponding Author
Masashi Aoki MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Correspondence to: M. Aoki; e-mail: [email protected]Search for more papers by this authorTetsuya Akiyama MD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorHitoshi Warita MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorMasaaki Kato MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorAyumi Nishiyama MD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorRumiko Izumi MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorChikako Ikeda MD
Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
Search for more papers by this authorMasaki Kamada MD, PhD
Department of Neurological Intractable Disease Research, Kagawa University Faculty of Medicine, Kagawa, Japan
Search for more papers by this authorNaoki Suzuki MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Search for more papers by this authorCorresponding Author
Masashi Aoki MD, PhD
Department of Neurology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574 Japan
Correspondence to: M. Aoki; e-mail: [email protected]Search for more papers by this authorThis article was published online on 23 FEB 2016. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 09 AUG 2016.
This study was supported by grants-in-aid for research on rare and intractable diseases; the Research Committee on Establishment of Novel Treatments for Amyotrophic Lateral Sclerosis; grants-in-aid from the Research Committee of CNS Degenerative Diseases of the Ministry of Health, Labour and Welfare of Japan; grants for research on nervous and mental disorders (20B-13), measures for intractable disease, and psychiatric and neurological disease and mental health; and grants-in-aid for scientific research (25293199 and 26461288) from the Japanese Ministry of Education, Culture, Sports, Science and Technology. The HGVD database was supported by a research grant (201238002A) for intractable diseases from the Ministry of Health, Labour and Welfare of Japan.
ABSTRACT
Introduction: We investigated possible genotype–phenotype correlations in Japanese patients with familial amyotrophic lateral sclerosis (FALS) carrying fused in sarcoma/translated in liposarcoma (FUS/TLS) gene mutations. Methods: A consecutive series of 111 Japanese FALS pedigrees were screened for copper/zinc superoxide dismutase 1 (SOD1) and FUS/TLS gene mutations. Clinical data, including onset age, onset site, disease duration, and extramotor symptoms, were collected. Results: Nine different FUS/TLS mutations were found in 12 pedigrees. Most of the patients with FUS/TLS-linked FALS demonstrated early onset in the brainstem/upper cervical region, and relatively short disease duration. A few mutations exhibited phenotypes that were distinct from typical cases. Frontotemporal dementia was present in 1 patient. Conclusions: This study revealed a characteristic phenotype in FUS/TLS-linked FALS patients in Japan. FUS/TLS screening is recommended in patients with FALS with this phenotype. Muscle Nerve 54: 398–404, 2016
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