Novel Variants in the FIG4 Gene Associated With Chinese Sporadic Amyotrophic Lateral Sclerosis With Slow Progression

Background@#and Purpose Mutations in the FIG4 gene have been linked to amyotrophic lateral sclerosis (ALS) type 11 in Caucasian populations. The purpose of this study was to identify FIG4 variants in a cohort of 15 familial ALS (FALS) indexes and 275 sporadic ALS (SALS) patients of Han Chinese origin. @*Methods@#All 23 exons of FIG4 were sequenced using targeted next-generation sequencing.An extensive literature review was performed to detect genotype-phenotype associations of FIG4 mutations. @*Results@#No FIG4 variants were identified in the FALS patients. One novel heterozygous missense variant (c.352G>T [p.D118Y]) and one novel heterozygous nonsense variant (c.2158G>T [p.E720X]) in FIG4 were identified in two SALS patients. The p.E720X variant is interpreted as likely pathogenic while the p.D118Y variant is a variant of uncertain significance. The patient carrying the p.E720X mutation developed lower-limb-onset slowly progressive ALS, and survived for 11.5 years. The patient harboring the FIG4 p.D118Y variant also presented with progressive ALS, with the score on the ALS Functional Rating Scale–Revised (ALSFRS-R) decreasing by 0.4 per month. The rate of decrease in the ALSFRS-R scores from symptom onset to diagnosis seemed to be lower in the patients carrying FIG4 variants than the no-FIG4-mutation ALS patients in this study. @*Conclusions@#Our findings suggest that ALS patients carrying FIG4 mutations are not common in the Chinese population and are more likely to exhibit slow progression.

Evaluation of brain dysfunction in chronic anoxic encephalopathy with evoked potentials / 中国应用生理学杂志

<p><b>AIM</b>To explore the relationship between evoked potentials (EPs) and chronic anoxic brain damage by chronic intermittent hypoxia (CIH), and provide theory evidence for diagnosis and treatment of anoxic encephalopathy.</p><p><b>METHODS</b>BAEP and SLSEP were recorded in rat model with CIH (hypoxia group) and rat with normoxia (normal group). Morris water maze was used to observe learning and memory ability. Immunohistochemical method was used to investigate the expression levels of caspase-3 in brain tissue.</p><p><b>RESULTS</b>The peak latency (PL) of wave I, III, V and the interpeak latency (IPL) of wave III - V, I - V in BAEP in hypoxia group were much longer than that of in normal group (P < 0.05). The PL of wave N1, P1 of SEP in hypoxia group were much longer than that of in normal group (P < 0.05). In the water mase test, the escape latency (EL) of hypoxia group was much longer than normal group (P < 0.01). The number of caspase-3 positive cells in hypoxia group was much larger than that of in normal group (P < 0.05). There was a positive correlation among BAEP, SLSEP, the number of caspase-3 positive neuron and EL of water mase.</p><p><b>CONCLUSION</b>The alteration of BAEP and SLSEP has an apparent correlation with chronic anoxic brain damage. This provides theory evidence for diagnosis and treatment of anoxic encephalopathy.</p>