We previously identified optineurin (OPTN) as a novel causal gene

of amyotrophic lateral sclerosis (ALS).[1] OPTN mutations result in autosomal dominant and recessive traits. For example, an E478G mutation is considered to result in dominant inheritance, and Q398X recessiveness. Elucidating the clinicopathological features of ALS associated with OPTN mutations (OPTN-ALS) could help interpret the role of OPTN in ALS pathogenesis. Recently, we described the clinicopathology of a family with the heterozygous selleck kinase inhibitor E478G OPTN mutation, which showed widespread transactivation response (TAR) DNA-binding protein 43 (TDP-43) pathology.[2] Here we report the clinicopathological findings of two ALS patients homozygous for the Q398X OPTN mutation. A 52-year-old Japanese woman presented with progressive bulbar palsy. Her medical history was significant

CT99021 cell line for glaucoma. Her parents were first cousins. She had no family history of either neurological diseases or glaucoma. Most of the patient’s reflexes presented a hyper response; the snout reflex was the only pathological reflex present. The patient was diagnosed with possible ALS with bulbar onset, according to the revised El Escorial criteria. She later developed symptoms of forced crying and laughter, and marked deformity of the hands, possibly because of dystonia (Fig. 1A). Brain MRI revealed temporal lobe and motor cortex

atrophy (Fig. 1B,C). Phosphatidylinositol diacylglycerol-lyase The patient died of respiratory failure at age 61 and an autopsy was performed. A 44-year-old Japanese woman presented with right upper limb weakness and atrophy. She had no history of glaucoma. Her family history was negative for neurological diseases and glaucoma. Her parents were not consanguineous. The patient’s reflexes presented a hyper response in the lower extremities and no pathological reflexes were present. Her cognitive function was normal. Needle electromyography showed both active and chronic denervation in the cervical, thoracic, lumbosacral and bulbar regions. These results supported the diagnosis of laboratory-supported probable ALS according to the revised El Escorial criteria. The patient died of respiratory failure at age 48 and autopsy was not performed. This study was approved by the ethics committee of The Tokushima University Hospital and all participants provided written informed consent. We previously isolated DNA from the venous blood of ALS patients and detected a homozygous Q398X in the OPTN gene.[1] A haplotype region of 0.9 megabases that contained the OPTN gene was found to be shared by patients.[1] Mutations of SOD1, TARDBP, FUS, VAPB, ANG, Dynactin, CHMP2B, STXN, in Patient 1 and SOD1, TARDBP, FUS in Patient 2 were excluded.