A de novo variant of POLR3B causes demyelinating Charcot-Marie-Tooth disease in a Chinese patient: a case report.

BACKGROUND: Charcot-Marie-Tooth (CMT) disease is a group of inherited peripheral neuropathies, which are subdivided into demyelinating and axonal forms. Biallelic mutations in POLR3B are the well-established cause of hypomyelinating leukodystrophy, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism. To date, only one study has reported the demyelinating peripheral neuropathy phenotype caused by heterozygous POLR3B variants. CASE PRESENTATION: A 19-year-old male patient was referred to our hospital for progressive muscle weakness of the lower extremities. Physical examination showed muscle atrophy, sensory loss and deformities of the extremities. Nerve conduction studies and electromyography tests revealed sensorimotor demyelinating polyneuropathy with secondary axonal loss. Trio whole-exome sequencing revealed a de novo variant in POLR3B (c.3137G > A). CONCLUSIONS: In this study, we report the case of a Chinese patient with a de novo variant in POLR3B (c.3137G > A), who manifested demyelinating CMT phenotype without additional neurological or extra-neurological involvement. This work is the second report on POLR3B-related CMT.

[The significance of quantitative temperature sense thresholds in diagnosis of small fibrous sensory neuropathy in patients with type 2 diabetes].

OBJECTIVE: To evaluate the small fiber function in patients with type 2 diabetes mellitus of the early stage by measuring the sensory threshold with the quantitative temperature testing technology. METHODS: Twenty cases of patients with type 2 diabetes with no neurological deficit (DM group) and twenty age and sex-matched healthy controls underwent the detecting of cold sensory threshold (CST), warm sensory threshold (WST), cold pain threshold (CPT), heat pain threshold (HPT) in both inside of their hands. RESULTS: There was no significant difference in CST, WST, CPT and HPT between left and right inside of hand of the same sample among all the testers. But the four kinds of threshold showed significant difference in the right inside of hand between patients and healthy people ( P < 0.05). In addition, the CST and WST differed significantly in the left inside of hand between the patients and healthy controls while the CPT and HPT showed no significant difference in the left inside of hand between them. Patients group and control group with CST and WST on the left side of the comparison difference was statistically significant (P < 0.05). CONCLUSION: Quantitative analysis of temperature sense threshold can not only reflect increase of the pain threshold value, also can reflect its decrease, i. e. hyperalgesia, which may help to diagnose small fibrous peripheral neuropathy recognition, especially in early diabetic peripheral neuropathy.

Fine mapping and whole-exome sequencing of a familial cortical myoclonic tremor with epilepsy family.

Familial cortical myoclonic tremor with epilepsy (FCMTE) is an autosomal dominant epilepsy syndrome. Four loci, including 8q24 (FCMTE1), 2p11.1-q12.2 (FCMTE2), 5p15.31-p15.1 (FCMTE3), and 3q26.32-3q28 (FCMTE4) were previously reported. Herein, we report a new FCMTE1 pedigree from Chinese population with its clinical and genetic study results. Whole genome scan was performed to identify the causative gene region and copy number variants. Whole-exome sequencing was used to identify the causative gene. There were twelve affected members alive in this FCMTE1 pedigree. Nine affected members had both cortical myoclonic tremor and epilepsy, while three affected members had only cortical myoclonic tremor. Electrophysiologic examinations manifested giant somatosensory evoked potentials and long-latency cortical reflex in some affected members. Whole genome scan identified a 20.4 Mb causative gene region at 8q22.3-q24.13. No copy number variants were identified as the causative mutation. Whole-exome sequencing identified a co-segregated mutation (c.206A>T; p.Y69F) in the SLC30A8 gene. However, the evidence supporting this gene as the causative gene of FCMTE1 is not enough. We report the first Chinese FCMTE1 pedigree. No copy number variants, point mutation or small insertion/deletion were detected in the identified region that showed an association with FCMTE1. Further studies could focus on other possible genetic mechanisms while the association between the SLC30A8 and FCMTE1 needs further evidence.

[Event-related potentials P300 with memory function and psychopathology in first-episode paranoid schizophrenia].

OBJECTIVE: To investigate the variability of event-related potentials P(300) and the relationship with memory function/psychopathology in patients with first-episode paranoid schizophrenia. METHODS: Thirty patients with first-episode paranoid schizophrenia (patient group) and twenty health subjects (control group) were enrolled in the study. The auditory event-related potentials P300 at the scalp electrodes Cz, Pz and Wechsler Memory Scale (WMS) were examined in both groups, Positive And Negative Syndrome Scale (PANSS) was evaluated in patient group. RESULTS: In comparison with control group, patients had longer latency of P300 [(390.6 ± 47.6)ms at Cz and (393.3 ± 50.1)ms at Pz] (P<0.01), lower amplitude of P300 [(7.7 ± 3.4) µV at Cz and (8.5 ± 3.9)µV at Pz] (P<0.05-0.01). The memory quotient (88.1 ± 10.0) scores and short-term memory, immediate memory in patient group were damaged significantly (P<0.05-0.01). In patient group, the latency of P300 was correlated positively with PANSS scores and negatively with WMS scores (P<0.05-0.01). CONCLUSION: First-episode paranoid schizophrenia has memory deficit, which can be evaluated comprehensively by P300 and WMS. The longer latency of P300 might be associated with the increased severity of first-episode paranoid schizophrenia.

[Clinical and genetic analysis of a pedigree of myotonic dystrophy disease].

OBJECTIVE: To investigate the clinical manifestations and to make genetic analysis in a pedigree with myotonic dystrophy disease. METHODS: The proband and available family members were identified by neurological examination. The clinical manifestation of 8 patients (including the proband) was analyzed; the electromyographic data of 5 patients were compared with 6 other family members. Blood samples were obtained from the 7 patients of the family (excepting II6). DM(1) and DM(2) gene were amplified by PCR, tested by agarose electrophoresis, then analyzed by genetic analyzer. RESULTS: Myotonia and muscle weakness were the main manifestations associated with heart block (7/8) and cataract(6/7). Electromyologram showed myopathic abnormalities not only in patients but also in other members of the family (5/6). The CTG repeats in DM1 and CCTG repeats in DM2 were all in normal range. CONCLUSION: There likely to be new mutants in this DM pedigree and further study is needed.

[Study of the neuropsychology and aural event related evoked potential on patients with the infarction in basal ganglia region].

AIM: To learn the condition of the memory and the visual space of the patient who has suffered from the infarction in basal ganglia region, and to analyze its impact on and the characteristics of the patients' cognition. METHODS: By testing respectively on 21 subjects who were initially infarcted in basal ganglia with single focus on one side, and 21 healthy volunteers with corresponding age, gender and educational background with Rey-Osterrieth Complex Figure Scale (Rey), Clinical Memory Scale (CMS), Hospital Anxiety-Depression Scale (HAD), National Institute of Health Stroke Scale (NIHSS), Oxford Handicap Scale (OHS), Barthel Index (BI), and Aural Event Related Evoked Potential (AERP) as well. RESULTS: Compared with the control group, the patient group got higher scores of anxiety and depression in HAD), which showed absolutely statistical significance; they demonstrated longer reaction time in AERP, which also showed statistical significance; and in CMS. they displayed inferior performance in the free picture recall and the memory quotient (MQ), which again had statistical significance. However, compared with the control group, the patient group got scores with no significance in copy, immediate recall and delayed recall in Rey. CONCLUSION: The infarction in basal ganglia region with single focus on one side may impact on the patient's executive function, memory function and emotion. But no impact is showed on patient's visual space function.