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.

Analysis of CLCN1 gene mutations in 2 patients with myotonia congenita / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate chloride channel 1 (CLCN1) gene mutation and clinical features of 2 Chinese patients with myotonia congenita.</p><p><b>METHODS</b>Clinical data of a patient from a family affected with myotonia congenita in addition with a sporadic patient from Fujian province were analyzed. Exons of CLCN1 gene were amplified and sequenced.</p><p><b>RESULTS</b>The proband from the affected family was found to carry a c.1024G>A heterozygous missense mutation in exon 8, whilst the sporadic patient has carried a c.1292C>T heterozygous missense mutation in exon 11.</p><p><b>CONCLUSION</b>Detection of CLCN1 gene mutation is an effective method for the diagnosis of myotonia congenita. Exon 8 of CLCN1 gene may be a mutational hotspot in Chinese patients with myotonia congenita.</p>

Correlation analysis of cognitive function and changes in proton magnetic resonance spectroscopy of the hippocampus in patients with complex partial seizures / 中华神经医学杂志

Objective To investigate the features of cognitive impairment in patients with complex partial seizures (CPS) and the correlation between the cognitive function and proton magnetic resonance spectroscopy (~1H-MRS). Methods Forty-five patients with CPS and 16 healthy controls were examined by the following means: memory function examination by the clinical memory scale, intelligence function examination by Ravin's standard progressive Matrices (R'SPM) and ~1H-MRS scan in the bilateral hippocampus. Memory quotient (MQ), Intelligence quotient (IQ), the levels ofNAA, Cho, Cr and the ratio of NAA/Cr+Cho were compared between the two groups. Meanwhile, the correlation coefficients were calculated. Results The scores of pointing memory, associational learning, image free memory, association memory of portrait and MQ except insignificant figure recognition were significantly lower in patients with CPS than those in the control group (P<0.05); the scores of Ravin's standard progressive matrices and IQ were noticeably lower in patients with CPS than those in the controls. The levels of NAA, Cho, Cr and the ratio of NAA/Cr+Cho in patients with CPS were significantly lower than those in the controls (P<0.05). Patients with CPS showed positive correlation between MQ and the level ofNAA, MQ and the ratio ofNAA/Cr+Cho, IQ and the level of NAA, as well as IQ and the ratio ofNAA/Cr+Cho (P<0.05); while level of Cho and both MQ and IQ were in inverse proportion (P<0.05) and no correlation between the lever of Cr and both MQ and IQ was found in patients with CPS (P>0.05). Conclusions The patients with CPS do have the cognitive impairment including short-term memory deficit and the decreased ability of abstraction, maturity judgment and reasoning. The correlation between cognitive function and the levels ofNAA, Cho, Cr and the ratio of NAA/Cr+Cho indicated that ~1H-MRS can check the cognitive function of patients with CPS in early stage objectively. Together with neuropsychology examination, ~1H-MRS can detect the disturbance of cognitive function in the patients with CPS precisely in early stage.