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

: 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