Genotype–phenotype relationships in familial amyotrophic lateral sclerosis with FUS/TLS mutations in Japan

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.