Autosomal recessive cerebellar ataxias are a group of neurodegenerative disorders that are characterized by complex clinical and genetic heterogeneity. Although more than 20 disease-causing genes have been identified, many patients are still currently without a molecular diagnosis. In a two-generation autosomal recessive cerebellar ataxia family, we mapped a linkage to a minimal candidate region on chromosome 16p13.3 flanked by single-nucleotide polymorphism markers rs11248850 and rs1218762. By combining the defined linkage region with the whole-exome sequencing results, we identified a homozygous mutation (c.493CT) in CHIP (NM_005861) in this family. Using Sanger sequencing, we also identified two compound heterozygous mutations (c.389AT/c.441GT; c.621C>G/c.707GC) in CHIP gene in two additional kindreds. These mutations co-segregated exactly with the disease in these families and were not observed in 500 control subjects with matched ancestry. CHIP colocalized with NR2A, a subunit of the N-methyl-D-aspartate receptor, in the cerebellum, pons, medulla oblongata, hippocampus and cerebral cortex. Wild-type, but not disease-associated mutant CHIPs promoted the degradation of NR2A, which may underlie the pathogenesis of ataxia. In conclusion, using a combination of whole-exome sequencing and linkage analysis, we identified CHIP, encoding a U-box containing ubiquitin E3 ligase, as a novel causative gene for autosomal recessive cerebellar ataxia.

Folate supplementation can reduce the incidence of hepatotoxicity and gastrointestinal side-effects of MTX in patients with RA. It can also reduce patient withdrawal from MTX treatment. Although it tended to reduce mouth sores, it had no statistical significance. No significant difference was found between high-dose folate and low-dose folate on MTX efficacy or toxicity.

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The study aimed to investigate the expression and significance of the plasma let-7 family in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Blood samples from 5 anti-NMDAR encephalitis patients and 5 negative controls were collected for microarray analysis. Blood samples from10 anti-NMDAR encephalitis patients, 10 anti-NMDAR encephalitis patients whose physical conditions have improved after 3 months of immunotherapy, 20 virus (meningitis) encephalitis patients, 20 tuberculosis (meningitis) encephalitis patients, 10 purulent (meningitis) encephalitis patients, 20 cerebral cysticercosis patients, 20 ischemic stroke patients, 20 intracerebral hemorrhage patients, 15 neuromyelitis optica patients, 15 multiple sclerosis patients, 15 moyamoya disease patients, and 20 negative controls were collected for real-time quantitative PCR (qRT-PCR) analysis. The expression levels of let-7a, let-7b, let-7d, and let-7f were significantly down-regulated in anti-NMDAR encephalitis compared with the negative controls (NC). The expression levels of let-7a, let-7d, and let-7f were significantly down-regulated in other nervous system diseases compared with the NC group while the expression level of let-7b was statistically insignificant in other nervous system diseases compared with the NC group. In addition, there was no significant dysregulation of let-7b in the anti-NMDAR encephalitis treatment group compared with the NC. Let-7b may be a potential diagnostic marker and an indicator that reflected the molecular mechanism of anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a new category of autoimmune encephalitis associated with anti-NMDA receptor antibodies. The disease was first described in 2007, and it predominantly affects young women with or without ovarian teratomas. Most patients typically present with seizures, a decreased consciousness level, dyskinesia, autonomic dysfunction, and psychiatric symptoms. The presence of anti-thyroid antibodies in non-tumor-associated anti-NMDA receptor encephalitis was first described in 2010. Additionally, anti-thyroid antibodies were found in teratoma-associated anti-NMDA receptor encephalitis. We report the cases of 3 Chinese girls with non-tumor-associated anti-NMDA receptor encephalitis with positive anti-thyroid antibodies. We followed up the details of their titers and suggest that anti-thyroid antibodies were an indicator of autoimmune predisposition in the development of non-tumor-associated anti-NMDA receptor encephalitis.