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Objective:To investigate the genetic distribution of pathogenic genes of Charcot-Marie-Tooth diseases (CMT) in Chinese Han population, and compare the similarity and difference with the data in Peking University Third Hospital in 2013.Methods:Five hundred and twenty families with CMT and related diseases in Peking University Third Hospital and China-Japan Friendship Hospital from January 2007 to March 2021 were collected. After peripheral myelin protein 22 (PMP22) gene duplication and deletion mutations were initially detected by multiple ligation probe amplification, the probands of these families were sequenced by next-generation sequencing (NGS) gene panel or whole exome sequencing, and validated by Sanger sequencing.Results:Among the 520 families, 336 CMT families were genetically confirmed, and the mutation detection rate increased from 48.6% (51/105) in 2013 to 64.6% (336/520) in 2021 (χ 2=9.54, P=0.003). Among them, 139 families had PMP22 gene duplication mutation (139/520, 26.7%), 46 families had gap junction beta-1 (GJB1) gene mutation (46/520, 8.8%), 26 families had mitofusin-2 (MFN2) gene mutation (26/520, 5.0%), 12 families had myelin protein zero (MPZ) gene mutation (12/520, 2.3%), 11 families had PMP22 gene point mutation (11/520, 2.1%), and 10 families had heat shock protein B1 gene mutation (10/520, 1.9%). There were 10 families with ganglioside induced differentiation associated protein 1 (GDAP1) gene mutation (10/520, 1.9%), 8 families with SH3 domain and tetratricopeptide repeats 2 (SH3TC2) gene mutation (8/520, 1.5%), 7 families with immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene mutation (7/520, 1.3%), 6 families with MORC family CW-type zinc finger 2 (MORC2) gene mutation (6/520, 1.2%), 5 families with sorbitol dehydrogenase (SORD) gene mutation (5/520, 1.0%), 16 families with very rare gene mutation (16/520, 3.1%) and 184 families without genetic diagnosis (184/520, 35.4%). Conclusions:Compared with the results in 2013, the 3 most common genes affecting CMT were still PMP22, GJB1 and MFN2 genes, but the proportion difference of patients with MPZ gene mutation gradually decreased with other genes such as SH3TC2 and GDAP1 genes. The proportion of newly discovered CMT genes, such as MORC2 and SORD genes, was similar with IGHMBP2 gene, which should be paid more attention. NGS greatly improved the detection rate of CMT, especially for patients with autosomal recessive-CMT.
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A 14-year-old male pediatric patient was admitted to the hospital mainly because of neck and back deformity, with limited activity for 7 yr, dysphagia and short of breath for more than 10 months.He was diagnosed with cervical lordosis deformity, RyR1 gene-related myopathy, high possibility of multi-minicore disease and being susceptible to malignant hyperthermia.Posterior cervical orthopedic internal fixation surgery was successfully performed under total intravenous anesthesia with propofol.The vital signs were stable during anesthesia and operation which lasted for 10 h. The patient was admitted to intensive care unit after the uneventful operation.When emerging from general anesthesia, the patient suddenly presented with symptoms of muscular fasciculation in the head, face, trunk and limbs, along with elevated body temperature as high as 39.4℃, severe acidosis and hypercapnia, meanwhile, the blood creatine kinase, blood myoglobin and urinary myoglobin gradually increased.The patient was diagnosed with malignant hyperthermia based on the clinical grading scale score of 63.Dantrolene sodium was infused intravenously, combined with multiple treatments such as physical cooling, correction of acidosis and electrolyte disturbance, alkalization of urine, intermittent hemofiltration and plasma exchange.The arrhythmia and delirium were treated symptomatically.The pediatric patient was fully recovered and discharged with good outcomes.
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Objective To explore the diagnostic value of tremor analysis in patients with coexisting essential tremor (ET) and Parkinson's disease (PD).Methods A cross-sectional survey was conducted to collect 30 patients with PD,30 patients with ET and 20 patients with ET + PD in Peking University Third Hospital from January 2015 to December 2017.Tremor analysis was performed in all the patients.Results There were statistically significant differences in age (63.0(54.8,68.0),49.0(26.5,58.5),57.0(50.0,66.0) years,H=21.336,P＜0.05),disease course (12.0(8.0,13.3),36.0(12.0,87.0),22.0(11.5,33.0) years,H=18.233,P＜0.05) and Unified Parkinson's Disease Rating Scale score (21.13± 8.85,8.00± 3.68,24.35±9.14,F=36.443,P＜0.05) among the PD,ET and ET+PD groups.The average tremor frequencies in PD,ET and ET+PD groups at rest were (5.46±0.77),(7.11 ± 1.80) and (6.18± 1.55) Hz,respectively,with statistically significant differences among the three groups (F=5.77,P=0.006).The average tremor frequencies in the three groups at posture were (6.19±2.21),(8.23± 1.96) and (6.49± 1.23) Hz,respectively,with statistically significant differences (F=9.673,P＜0.01).There was no statistically significant difference in tremor amplitude among the three groups at rest and posture position.In the PD,ET and ET+PD groups,the proportion of electromyography alternating contractions of the active and antagonistic muscles was 76.9％(20/26),0/6 and 5/15 at rest (x2=17.192,P＜0.01),and 53.8％ (14/26),20.0％ (6/30) and 4/15 at posture (x2=7.564,P=0.023),both with statistically significant differences.Conclusions The clinical manifestations of patients with ET+PD have both characteristics of PD and ET,but they have their own characteristics.Tremor analysis can objectively identify the bilaterally synchronous or alternate discharges of electromyography at rest,which are different from those of typical PD and ET.Tremor analysis is helpful for the identification of this disease.
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Objective To characterize the clinical,electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM).Methods We retrospectively analyzed the clinical,electrophysiology,neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014).Results Among these 4 patients,2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months.Two patients were with acute onset and 2 with chronic onset.All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration.One patient had interstitial lung disease.The anti-signal recognition particle antibodies were strong positive in all 4 patients.Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients.Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients.However,very few inflammatory cells were detectable in patients.One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs.Conclusions IMNM is characterized by heterogeneity at disease onset,severity and ilnvolvement of muscles with,however,similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation.Corticosteroid and/or immunosuppressant is effective for patients.
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Objective To investigate effect of genetic variants in angiogenin (ANG) on the susceptibility of familial amyotrophic lateral sclerosis (FALS) in Han Chinese.Methods Thirty-one FALS families from 2009 to 2012 were collected and ANG gene was screened in the probands using PCR and direct sequencing.Results All 31 ALS families were autosomal dominant inheritance.No mutations and single nucleotide polymorphism were detectable in ANG gene in the 31 probands.Conclusion Our study suggests that ANG gene variations may be rare in Chinese Han FALS.
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Objective To summarize the clinical features,electrophysiology and neuropathological characteristics of peripheral nerves in patients with vasculitic neuropathy.Methods We retrospectively analyzed the clinical,electrophysiology and neuropathological characteristics of 15 patients with vasculitic neuropathy who underwent electrophysiology and sural nerve biopsy in our department from January 2009 to June 2013.Results There were 8 males and 7 females,aged from 38 to 82 years old,with a peripheral neuropathy course ranged from 0.5 month to 60 months.In the total of 15 patients,3 patients were diagnosed as nonsystemic vasculitic neuropathy,while the other 12 patients were diagnosed as systemic vasculitis neuropathy (SVN) including 5 cases of primary systemic vasculitis and 7 cases of secondary systemic vasculitis.In patients diagnosed as primary systemic vasculitis,there were 2 cases of Churg-Strass syndrome (CSS) and 3 cases of ANCA associated vasculitis.In patients diagnosed as secondary systemic vasculitis,there were 1 case of systemic lupus erythematosus (SLE),2 cases of sicca syndrome (SS),3 cases of rheumatoid arthritis (RA),1 case of Behcet' s disease associated with thyroid papillary carcinoma,1 case of hepatitis B and 1 case of RA-associated SS.For the pathological features of vasculitic neuropathy,type 1 lesion was found in 4 patients,type 2 lesion in 2 patients,and type 3 lesion in 9 patients.Axon degeneration was observed in 8 patients,while 7 patients manifested as axon degeneration associated with demyelination and local thickening of the perineurium was found in 2 patients.Conclusion Multiple mononeuropathy and asymmetric polyneuropathy are the common clinical presentations of vasculitic neuropathy.Electrodiagnostic testing almost always reveals the evidence of a predominantly axonal and sensorimotor process with associated demyelination presented in some cases.Sural nerve biopsy showes changes indicative of an axonopathy.