Neuronal intranuclear inclusion disease revisiting / 中华神经科杂志

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease. Skin biopsy, as a screening method, has greatly improved the diagnostic efficiency of the disease. Recently, researchers have successfully identified that the GGC repeat expansion in the 5' region of the NOTCH2NLC gene is the causative mutation of NIID. In addition to the typical NIID phenotype presenting with episodic/progressive encephalopathy, peripheral neuropathy, and autonomic disturbance, the gene mutation had also been reported to be associated with a small portion of Alzheimer 's disease, Parkinsonism, multiple system atrophy and essential tremor patients. So, the name of NOTCH2NLC-related repeat expansion disorder was proposed to include these variable phenotypes. We revisited the discovery milestones, clinical phenotype, laboratory examinations, as well as new insight into diagnosis and treatment of NIID.

Clinical features of familial idiopathic basal ganglia calcification caused by a novel mutation in the SLC20A2 gene / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To describe clinical and genetic feature in a Chinese family with familial idiopathic basal ganglia calcification 3 (IBGC-3) caused by a novel mutation in the SLC20A2 gene.</p><p><b>METHODS</b>Clinical data was collected from a family with familial IBGC-3. All of the family members underwent cerebral CT. Potential mutation of the SLC20A2 gene were screened in the proband, 5 symptomatic patients, 5 asymptomatic family members, and 100 healthy Chinese controls. Exon 8 of the SLC20A2 gene was cloned into plasmid and sequenced.</p><p><b>RESULTS</b>There were 6 symptomatic patients (3 males and 3 females) in an autosomal dominant pedigree. The patients manifested as juvenile-onset paroxysmal kinesigenic dyskinesia, in addition to pyramidal signs in proband. 5 patients alive had calcification in bilateral basal ganglia and subcortical areas. One asymptomatic member also had calcification in the brain; and 2 cases of asymptomatic young members had bilateral globus pallidus calcification. A novel c.1086delC mutation in SLC20A2 gene has been identified in proband and 7 family members with intracranial calcification. The deletion mutation was not found in 2 family members without intracranial calcification and healthy controls members. There is no clear relationship between clinical symptoms and the severity of calcification in cerebral CT.</p><p><b>CONCLUSION</b>Familial idiopathic basal ganglia calcification caused by the SLC20A2 gene mutation can manifest as juvenile onset paroxysmal kinesigenic dyskinesia. Further study should be done to validate the unrelated relationships between the severity of calcification in IBGC 3 cranial CT and clinical symptoms.</p>

Clinical features, radiological characteristics, and pathological changes in 42 patients with cerebral sparganosis / 中华神经科杂志

Objective To investigate the clinical features,the radiological characteristics,and the pathological changes of cerebral sparganosis.Methods We retrospectively collectted and summarized the clinical data of 42 patients with cerebral sparganosis from the Iinstitute of Anti-parasitic Diseases of Jiangxi Province and the First Affiliated Hospital of Nanchang University during January 2000 to January 2014.The follow-up period of the 42 patients ranged from 4 to 96 months.Results Forty-two cases (30 males and 12 females) with cerebral sparganosis were enrolled in the study.Among the 42 patients,34 cases suffered from seizures,16 cases experienced headaches,and 14 cases had limb weakness.The brain CT scan showed the small and punctuate calcifications scattering around the lesions in 18 cases.The features of enhanced MRI included aggregating ring-like enhancement in 38 cases,tunnel lesions in 14 cases,and lesion migration in 13 cases.Twenty-four of the 42 patients were performed surgery.The brain tissues revealed multiple inflammatory tunnels,in which live or degenerated larvae were identified in 20 cases,but only eosinophilia tunnels were observed in the other 4 cases.The serum and cerebro-spiral fluid specimens from 18 patients without surgery were positive to spirometra mansoni antigen.Their cerebral lesions disappeared and got a favorable prognosis after administration of praziquantel in long term follow-ups.Conclusions There is a high incidence of cerebral sparganosis in Poyang lake basin.The clinical features of cerebral sparganosis mainly include seizure,headache and hemiparesis.The enhanced lesions show knot or tunnel signs on multi-planar MRI which are associated with the multiple inflammatory tunnels of larvae migration.A longterm administration of high dose opraziquantel can also get a good treatment prognosis without the classical surgical therapy for cerebral sparganosis.

Risk factors for in-hospital ischemic stroke in the Department of Cardiology: a retrospective case-control study / 国际脑血管病杂志

Objective To investigate the clinical features,etiology and risk factors of the inpatients with ischemic stroke in the Department of Cardiology.Methods The medical records of the inpatients with ischemic stroke and the inpatients in a control group were collected retrospectively.The demographics,vascular risk factors,clinical features,and other related factors were compared in both groups.Multivariate logistic regression analysis was used to analyze the independent risk factors for in-hospital ischemic stroke in the Department of Cardiology.Results A total of 2 789 inpatients in departments of cardiology were enrolled,and 26 of them (0.93％) had in-hospital stroke.One hundred thirty inpatients from 2 763 patients without in-hospital stroke were used randomly as control cases.The proportions of the inpatients of hypertension (73.08％ vs.50.77％ ; x2=4.348,P=0.037),atrial fibrillation (50.00％ vs.15.38％; x2=15.56,P=0.000),infection (30.77％ vs.7.69％ ; x2 =11.304,P =0.003),smoking (46.15％ vs.21.54％ ; x2 =6.886,P =0.009),alcohol (26.92％ vs.11.54％ ;x2 ＝ 4.233,P =0.040),previous stroke history (19.23％ vs.4.61％ ;x2 =7.062,P =0.008),and taking anti-hypertensive drugs (42.31％ vs.21.54％ ;x2 =4.985,P =0.026),as well as systolic blood pressure (143.43 ± 18.59 mm Hgvs.129.52 ± 23.52 mm Hg; t =3.209,P=0.003; 1 mmHg =0.133 kPa),diastolic blood pressure (88.77± 11.35 mm Hg vs.77.55± 14.60 mmHg; t=2.421,P =0.020),and homocysteine levels (19.27 ± 11.08 μnol/L vs.15.30 ±5.25 μmol/L; t =2.814,P =0.006) in the stroke group were significantly higher than those in the control group in the Department of Cardiology.Multivariate logistic regression analysis showed that atrial fibrillation (odds ratio [OR] 3.310,95％ confidence interval [CI] 1.207-9.076; P =0.020),infection (OR 3.270,95％ CI 1.024-10.438; P =0.045),systolic blood pressure (OR 1.023,95％ Cl 1.002-1.045; P =0.031),and homocysteine level (OR 1.089,95％ CI 1.009-1.175; P =0.029) were the independent risk factors for in-hospital ischemic stroke in the Department of Cardiology.Conclusions Atrial fibrillation,infection,systolic blood pressure,and high homocysteine levels are the independent risk factor for in-hospital ischemic stroke in the Department of Cardiology.Active intervention and control these risk factors may have great significance for reducing its risk.

Hemorrhagic transformation and outcomes in acute ischemic stroke: a retrospective case series study / 国际脑血管病杂志

Objective To investigate hemorrhagic transformation (HT) and outcomes in acute ischemic stroke.Methods The demographics,vascular risk factors,imaging and other clinical data in patients with acute ischemic acute were collected retrospectively and compared.Using the susceptibility weighted imaging (SWI) to diagnose HT,and the patients were divided into either a HT group or a non-HT group.The modified Rankin scale was used to evaluate the clinical outcomes.Multivariate logistic regression analysis was used to determine the independent risk factors for HT and poor outcome in HT patients.Results A total of 96 patients with acute ischemic stroke were enrolled and 34 of them had HT (35.4％).The age (66.21 ± 7.04 years vs.61.21 ±13.42 years; t =2.020,P=0.046) and infarct volume (3.88 ±2.20 cm3 vs.1.96 ± 1.37 cm3; t =5.67,P=0.001) in the HT group were significantly older or larger than those in the non-HT group.The proportions of hypertension (58.8％ vs.30.6％;x2 =7.228,P=0.007),diabetes (29.4％ vs.6.5％;x2 =9.293,P=0.002),atrial fibrillation (35.3％ vs.3.2％;x2=18.128,P=0.000),and cardiogenic cerebral embolism (35.3％ vs.3.2％ ; P =0.000) were significantly higher than those in the non-HT group,while the proportion of small arterial occlusive stroke was significantly lower than that in the non-HT group (38.2％ vs.62.9％ ;P =0.032).Multivariate logistic regression analysis showed that age (odds ratio [OR] 1.168,95％ confidence interval [CI] 1.059-3.412; P =0.021),infarct volume (OR 3.461,95 ％ CI 1.317-6.270; P =0.044) and atrial fibrillation (OR 1.284,95％ CI 1.117-2.903; P =0.015) were the independent risk factors for HT.In the HT patients,age (69.46 ±7.17 years vs.64.19 ±6.31 years; t =2.248,P =0.032) in the poor outcome group was significantly older than that in the good outcome group.The proportions of hypertension (84.6％ vs.42.9％ ;x2 =781,P =0.016),diabetes (50.0％ vs.14.3％ ;x2 =6.053,P =0.014),cardiogenic cerebral embolism (61.5％ vs.19.0％ ; P =0.025) and hematoma HT (76.9％ vs.19.0％ ;x2 =11.104,P =0.001) were significantly higher than those in the good outcome group.Multivariate logistic regression analysis showed that the diabetes (OR 2.151,95％ CI 1.179-3.218; P =0.023),atrial fibrillation (OR 4.136,95％ CI1.010 to 8.413; P =0.046) and hernatoma HT (OR 2.134,95％ CI 1.219-4.452; P =0.039) were the independent risk factors for the poor outcomes of HT patients at 3 months after symptom onset.Conelusions The incidence of HT in patients with acute ischemic stroke was 35.4％.Age,infarct volume and atrial fibrillation were the independent risk factors for HT,and diabetes,atrial fibrillation and hematoma HT were the independent risk factors for the poor outcomes in HT patients at 3 months after symptom onset.

Affected muscle fibers in Nonaka myopathy with endoplasmic reticulum stress / 中华神经科杂志

ObjectiveTo investigate the characteristic of pathology in Chinese patients with Nonaka myopathy.MethodsThirteen patients (7 males and 6 females) diagnosed with Nonaka myopathy in our laboratory from January 2002 to March 2011 were included in this study.Their mean age was 39.5 years old and the mean duration of illness was 4.15 years.The most common symptoms were weakness of raising feet with sparing of quadriceps femoris muscles in the early stage of disease.One patient presented the initial symptoms of upper limb weakness. Muscles biopsies were obtained from all these 13 patients. Histology study including immunohistochemical (IHC) staining with antibody against amyloid 3,phosphorylated tau protein,ubiquitin,glucose-regulated protein of molecular weight 78 000(GRP78),calnexin,caspase-12and Bax were performed.Skeletal muscle samples from 3 chronic fatigue syndrome patients,2 myofibrillar myopathy patients were used for control in the IHC staining. All coding exons of uridinediphospho-N-acetylglucosamine 2-epimerase gene were directly sequenced in genomic DNA from these patients.Results The main pathological changes of tibialis anterior muscle in 12 cases were muscle dystrophy with rimmed vacuoles.The rimmed vacuoles were positive for anti-β-amyloid,tau protein and ubiquitin in IHC studies.In the atrophy fibers,IHC showed the increased expression of endoplasmic reticulum stress related proteins GRP78 and calnexin,and apoptosis proteins of caspase-12 and Bax.ConclusionsThere is accumulation of abnormal proteins in muscle fibers in Chinese patients with Nonaka myopahty.These proteins may stimulate endoplasmic reticulum stress and apoptosis,which may be a mechanism responsible for muscle damage.

Myopathy with antibodies to the signal recognition particle: report of 8 cases / 中华风湿病学杂志

ObjectiveWe report the clinical and pathological features of 8 Chinese myopathy patients with antibodies to the signal recognition particle(SRP).MethodsSerum myositis antibody profiles were tested with immunoblotting.Muscle biopsies were performed for histological,enzyme histochemical and immunohistochemical stainings.The first antibody in the immunohistochemical staining was mouse anti-human monoclonal antibodies including CD8,CD20,CD68,MHC- Ⅰ and CD31.ResultsEight cases showed stark positive of anti SRP antibody,3 of them with positive anti Ro-52 antibody.The muscle biopsies showed necrotic and regenerative muscle fibers associated with infiltration of macrophage,but scattered T lymphocytes in 2 patients.Two of them presented with fiber hypertrophy and proliferation of connective tissue.There were some fibers with positive MHC-Ⅰexpression.Capillaries were almost normal.Conclusion The muscle weakness of myopathy with antibodies to SRP presents as a chronic progressive course and could associate with lung involvement.Fiber necrosis and regeneration are the main myopathological features,which can mimic muscular dystrophy in some cases.

The cfinical and pathological features of hypomyopathic dermatomyositis: a report of 6 cases / 中华风湿病学杂志

ObjectiveTo explore the clinical and pathological features of hypomyopathic dermatomyositis(HDM).MethodsSix cases of HDM among 62 cases of dermatomyositis diagnosed between January 2008 and June 2010 were collected and analyzed.Four were women and 2 were men.The age of onset was between 45 and 65 years old,with disease duration of more than 6 months.All HDM patients presented with DM-specific skin lesions,but without muscle weakness.Serum creatine kinase(CK) level was within normal limits in 5 and mild elevated in 1.Electromyogram showed myogenic changes in 4 cases and normal in the other 2 patients.Muscle biopsies were carried out in the left biceps branchii in all of them.The muscle sectionswereprocessedwithstandardhistologicalprocedures,enzymehistochemistricaland immunohistochemical stains were carried out.The antibodies used for immunohistochemical stains were antiCD8,anti-CD20,anti-CD68,and anti-MHC-Ⅰ monoclonal antibodies.ResultsMuscle biopsies showed a variable amount of macrophages and B-lymphocytes infiltrating in the peri-mysium and fascicle area.Three of them presented with mild peri-fascicular fiber atrophy with fiber necrosis and regeneration.Lipid droplets increased mildly in muscle fibers.Capillaries distributing around perifascicular regions were darkly stained in nonspecific esterase stain.Perifascicular fibers showed immune-reactivity to MHC-Ⅰantibody.Conclusion The myopathological changes of HDM mimic classical dermatomyositis in some cases.HDM might be an intermediate presentation between pure amyopathic dermatomyositis and classical dermatomyositis.

Novel mutation of HTRA1 gene causes cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy: one case / 中华神经科杂志

ObjectiveTo report a novel HTRA1 gene mutation caused cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) with migraine,urinary retention and constipation.MethodsThe patient was a 34-year-old woman who suffered from myalgia with cramp for 16 years,lumbago for 5 years,migraine and mild alopecia for 3 years,right hemiparesis for 5 months,and urinary retention and constipation for 1 month.Vertebral MRI showed degeneration of vertebral bodies with disc herniations.Brain MRI revealed diffuse white matter lesions and lacunar infarcts.Sural nerve and skin biopsies were performed in the patient. HTRA1 gene analysis was performed in patient,her parents and 2 brothers,and Notch3 gene analysis in the patient.ResultsThe sural biopsy demonstrated discontinuous of elastica internal with thickness of intima of arterioles.The capillary basement membranes were thickness with mini granular changes.A homozygous T to A transition at position 524( c.524T ＞ A) was found in HTRA1 gene.The heterozygous c.524T ＞ A mutation appeared in the parents and 2 brothers,but not in the controls.Notch3 mutations were not found in the patient. Conclusion CARASIL caused by novel homozygous c.524T ＞ A mutation of HTRA1 gene can present with migraine,urinary retention and constipation.

Clinical features of thyrotoxic periodic paralysis caused by inwardly rectifying potassium channel 18 gene mutations / 中华神经科杂志

Objective To report the clinical features and inwardly rectifying potassium channel 18 (KCNJ18) gene mutation in a group of patients with thyrotoxic periodic paralysis (TTP).Methods Fiftyseven TTP cases (55 male and 2 female) were collected in our clinic from July 2002 to October 2011.The KCNJ18 gene was directly sequenced in 57 TTP patients and 50 health Chinese controls through the nested PCR.According to the results of gene screening,the clinical features of KCNJ18 patients and non-KCNJ18 patients were retrospectively summarized and analyzed.Results In 4 male patients with TPP,we found 3 novel heterogeneous mutations (p.Q126X,p.K360T,p.E388K) and 1 reported mutation (p.A200P) in the KCNJ18 gene.The age of onset was 19-25 years old,and the duration ranged from 2 to 8 hours.The 4 patients all presented severe muscle weakness.The attacks of muscle weakness preceded overt symptoms of hyperthyroidism in the 4 patients. Three patients showed recurrent weakness during the 13-28 months follow-up,while the episodic weakness never appeared when patients got euthyroid. Conclusions The mutations in the KCNJ18 gene are responsible for a part of Chinese patients with TPP.The patients with KCNJ18 mutations have a shorter disease course,severer manifestation,and higher prevalence of recurrence as compared with those TPP patients without KCNJ18 mutations.

The inflammatory myopathy with abundant macrophages presenting with abundant foam cells: one case report / 中华神经科杂志

Objective To report the inflammatory myopathy with abundant macrophages presenting with abundant foam cells in a Chinese patient.Methods A 44 year-old man with rheumatoid arthritis manifested as progressive proximal muscle weakness in the upper limbs for 13 months and in the lower limbs for 11 months.Laboratory tests showed that serum creatine kinase level was increased,whereas neither the myositis antibody nor paraneoplasma antibodies were detectable,including anti-Jo-1 antibody.Electromyogram showed a classic myogenic pattern with irritable sarcomembrane excitement.Muscle biopsies were carried out in the left and right biceps brechii in 2 months and 13 months of the disease course respectively.The muscle sections were processed with standard histological,enzyme histochemistrical and immunohistochemical workup.Results The first muscle biopsy revealed CD8 positive T lymphocytes infiltrating into major histocompatibility complex (MHC)-Ⅰ positive fibers and distributing around endomysium,accompanied with scattered necrosis and regeneration.The second muscle biopsy showed perifascicular atrophy,fragmented perimysial connective tissue,and a large amount of CD68 positive foam cells and Touton cells accumulating within perimysial connective tissues and endomysium.Some CD20 positive B lymphocytes and plasmacytes were found around perivascular space,but CD8 positive T lymphocytes were only accumulated in the endomysium.MHC- Ⅰ was darkly expressed in the sarcolemma.Conclusions Inflammatory myopathy with abundant macrophages can present with foam cells infiltrating in perimysial and endomysium.The disease can be associated with rheumatoid arthritis and refractory to corticosteroid therapy.

A new MFN2 gene mutation resulting in hereditary motor and sensory neuropathy type 6, a family report / 中华神经科杂志

ObjectiveTo report clinical, pathological and molecular genetic features in a Chinese family with hereditary motor and sensory neuropathy type 6. MethodsThe index case is a 15 years old boy.He developed progressive distal limb weakness at the age of 5.The disease deteriorated slowly,accompanied with contracture of achilles' tendon. At the age of 11 years old he suffered from decrease of visual acuity. At the age of 12, he found the muscular atrophy of both hands without sensory disturbances.Visual evoked potential revealed prolonged latency of bilateral P100. Ophthalmological examination showed bilateral optic atrophy. His mother had the similar symptoms at the age of 7 and reduced visual acuity at the age of 10. Nerve conduction velocity revealed in both pat1ents no compound motor and sensory nerve action potentials in most nerves or slightly reduced nerve conduction velocities with severely reduced amplitudes of the compound motor and sensory nerve action potentials. Sural nerve biopsy was performed on the proband.The sequence of MFN2 gene was analyzed in DNA from the index, his mother and 100 healthy controls.ResultsSural nerve biopsy revealed severe loss of myelinated fibers with few regenerating clusters.Ultrapathological examination showed a few of atypical bulbs of myelinated fibers, occasionally regenerating clusters, mitochondrial swelling and aggregation in a few of axons. A new mutation of W740R mutation in MFN2 gene has been identified in the index case, her mother, but not in 50 healthy controls. Conclusions A novel MFN2 gene mutation result in hereditary motor and sensory neuropathy type 6.Mild visual loss appeares after the lesion of spinal nerves. Demyelination of peripheral nerve appears in the disease.

Mutant connexin 32 abnormally distributed in the vascular endothelial cells of X-linked Charcot-Marie-Tooth disease type 1 patients / 中华神经科杂志

ObjectiveTo investigate expression distribution of mutant connexin 32 (Cx32) protein in human endothelial cells in patients with X-linked Charcot-Marie-Tooth disease type 1 ( CMTX1 ) .MethodsNerve biopsies were performed in 3 patients with CMTX1 and in 3 non-CMTX1 controls. Cx32 mutations of c. 379A ＞ T( I127F), c. 533A ＞ G(D178G) and c. 590C ＞ T(A197V) were identified in these 3 patients respectively.Immunofluorescent (IMF) staining of nerve blood vessel was processed with antibodies against Cx32, Yon Willebrand factor and Cx40. The mutant Cx32 was constructed in pEGFP-N plasmid (pEGFP-N1-Cx32) and was transfected in HeLa cells. Cx32 and GRP78, a marker of endoplasmic reticulum ( ER), were stained by IMF in HeLa cells to investigate expression of mutant Cx32. ResultsIn 3 control cases, Cx32 was visualized by IMF staining as dots along gap junction of vascular endothelial cells,and it was coexisted with Cx40.However, immunoreactivity of Cx32 in 3 patients was predominantly decreased and was not located in endothelial gap junction. The transfection of 3 Cx32 mutants into HeLa cells demonstrated thepathogenic changes.The cells withthemutationc. 379A ＞T found Cx32 accumulations in the cytoplasm; the cells with mutation c. 533A ＞G showed few staining positive dots surrounding the nuclear and the cells with c. 590C ＞ T showed dot-like expression of Cx32 both in the cytoplasmicand cell membrane. The mutant Cx32 was not overlapped with expression of the marker of ER.ConclusionsMutant Cx32 might cause dysfunction of endothelial gap-junctions due to the abnormal expression of Cx32 in level and location in the vascular endothelial cells of CMTX1 patients.

Clinical and magnetic resonance imaging studies of Anderson-Fabry disease: 2 cases report / 中华神经科杂志

Objective To report 2 cases of Fabry disease with early-onset ischemic stroke and investigate the clinical and image features. Methods The 2 patients developed dizziness, diplopia and progressive memory decline at 32 and 25 years of age respectively. The α-galactosidase A (GLA)activity was 4. 3 U in case 1 and 1. 0 U in case 2 ( normal range 100-500 U). Skin biopsy showed numerous membrane bounded osmiophilic laminar material in vascular smooth muscle cells and endothelial cells. GLA gene analysis revealed GLA exon 7 1033-1034 TC del in case 1 and GLA exon 3 466G ＞ A in case 2. The 2 patients were evaluated by Mainz severity score index (MSSI) and cranial MRI. Results The general MSSI was 32 in case 1 and 16 in case 2, with the highest score of neurological score ( 11 and 14). Both cases showed multifocal infarcts in bilateral cerebellum, occipital lobe, basal ganglia, which were hypointensity on T1 WI and hyperintensity on T2WI. There were hyperintensity changes in the pulvinar and basal ganglia on T1 WI in case 2. Conclusions Cerebral ischemic stroke could appear as initial symptoms in Fabry disease,which predominantly involved the posterior circulation. There might be no dilation of basal-vertebral artery.

Hot spot mutations in electron transfer flavoprotein dehydrogenase gene of riboflavin responsive lipid storage myopathy in 20 Chinese families / 中华神经科杂志

Objective To report the spectrum of electron transfer flavoprotein dehydrogenase (ETFDH)gene mutations in 20 Chinese RR-LsM families.Methods Twenty-four RR-LSM patients in the First Hospital of Peking University from January 2003 to May 2010 were collected and the clinical characteristics were analyzed.These patients came from 20 families in North Mainland China.Sixteen families had 1 patient each.and the other 4 families had 2 patients.ETFDH gene analysis was performed in all patients,11 family members and 100 healthy controls.Results The mean onset age was(27.9±9.9)years.The main symptoms were limb weakness(21,87.5%),dysmasesia(15,62.5%),neck weakness (14,58.3%)and myalgia(14,58.3%).Eighteen patients had high level of acyleamitine.Fifteen of 17patients had glutaric aciduria.Seventeen ETFDH mutations,including 13 missense mutations,2 splice mutations,and 2 nonsense mutations,were identified in 19 families:c.998A>G,c.1450T>C,c.1703T>C,c.1717C>T,c.821G>A,c.643G>A,c.251C>T,c.1763A>T,c.IVS7+2T>C and c.IVS6+1G>A were Hovel mutations which were not found in 100 healthy controls.Nine families had the mutation of c.770A>G(P.Y257C)and 5 families had the mutation of c.1227A>C(P.L409F).Conclusions The numerous novel mutations in ETFDH gene indicate that Chinese RR-LSM might have special mutation pattern.c.770A>G(P.Y257C)and c.1227A>C(p.L409F)may be hot spot mutations in North Mainland China.

Phenotypic and genotypic studies in 6 Chinese Han families with oculopharyngeal muscular dystrophy / 中华神经科杂志

Objective To explore phenotypes and genotypes in 6 Chinese Han families with oculopharyngeal muscular dystrophy (OPMD).Methods There were 28 OPMD patients in 6 Chinese Han families, aged between 32 and 70 years old.The initial symptom was dysphagia in 13 patients, ptosis in 4 patients,lower limb weakness in 1 patient.Most OPMD patients displayed dysphagia and ptosis in 3-20 years after the initial symptom appeared.Biceps brachii biopsies were made in the 6 OPMD probands.The specimens were examined with histological, histochemical stainings and ultrastructural examination.The exon 1 of PABPN1 gene was sequenced in all probands of OPMD and some of their family members.Haplotype analysis was executed in the 6OPMD probands.Results Mild hypertrophy and hypotrophy of fibers and rimmed vacuoles were found in each probands of OPMD muscle biopsies.Intranuclear palisading filamentous inclusions only appeared in 4OPMD probands.Gene analysis identified (GCG)9 in exon 1 of PA BPN 1 gene was detected in 3OPMD families, while (GCG) 6 (GCA) 1 (GCG) 3, (GCG) 10 and (GCG) 8were in one family respectively.Two families with (GCG) 9 expansion shared a common rs2239579 (C) -(GCG) 9-SNP2622 (C) haplotype.Conclusions Dysphagia and ptosis may be the common initial symptoms in Chinese Han OPMD patients.Rimmed vacuoles and intranuclear inclusions may be the common pathological feature in the muscle fibers.Both (GCG) expansions and (GCA) insertion of PABPN1 gene could be detected in Chinese patients.The genetic heterogeneity and the haplotype of three (GCG)9 families in our patients indicate that OPMD arises from different origin within the Han population.Some families with the same (GCG)9 expansions probably come from a common ancestor.

Comparison of the clinical and magnetic resonance imaging characteristics of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy in mainland China and other countries / 中华神经科杂志

Objectives To analyse the clinical and MRI features of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL) in mainland China and compare these features with those reported in other countries.Methods All 26 CADASIL families were collected in First Hospital of Peking University from January 2003 to October 2009, and the diagnosis was confirmed by ultrastructural examination or Notch3 gene analysis.The age of onset, initial symptoms, main symptoms in 102 patients were described and the features with those reported in Germany, Japan, Arab and France were compared using x2 test.The cranial MRI changes in 35 patients were analysed and compared with the British and French patients.Results 102 patients had their initial symptoms between 22-80 years with the mean age of onset at (43.9 ± 11.0) years.There was no significant difference in the frequency of ischemic stroke or TIA (79.41% ) between our patients and the patients in other countries.Dementia rate (50.00% ) was significantly greater than that of Arab (21.05% ,x2 =5.513, P =0.020) and French patients(31.11%,x2 =4.517, P =0.034).The frequency of mood disturbances ( 14.71% ) was significantly lower than that of German patients (30.39% ,x2 =7.185, P =0.007).The frequency of migraine ( 13.73% ) was similar to that of France but lower than that of Japan (40%, x2 = 12.658, P = 0.000), Germany (38.24%, x2 =15.932, P=0.000) and Arab (42.11% ,x2 =6.869, P=0.009).Cranial MRIs were abnormal in all 35patients, but no lesion was seen in the medulla oblongata.Lacunar infarcts in the basal ganglia (82.86% )were significantly more frequent than that of French patients (60% , x2 = 5.663, P = 0.017).The frequency of leukoaraiosis in the cerebrum was similar to that of French patients.Anterior temporal involvement (68.57%) was significantly lower than of British patients ( 95%, x2 = 5.211, P = 0.022 ).Conclusion The clinical symptoms and MRI changes of CADASIL in different countries were not identical.Abnormal anterior temporal pole signal on MRI is not a sensitive marker for diagnosis of CADASIL in Chinese patients.

Clinical and pathological features of Danon disease associated with a novel lysosome-associated membrane protein-2B mutation / 中华神经科杂志

Objectives To report the clinical and myopathological features in a case with Danon disease caused by a novel mutation in the lysosome-associated membrane protein-2 ( LAMP2 ) B gene.Methods A 16-year-old boy presenting progressive muscle weakness and atrophy, accompanied with spinal ankylosis was clinically evaluated including electrocardiogram, echocardiogram and electromyogram.Muscle biopsy was carried out in the patient.The histological staining, ultrastructural examination, and immunohistochemical staining with antibodies against dystrophin, merosin and C5b9 were performed in frozen sections.LAMP2B sequence was analyzed in the patient and his parents.Results Electrocardiogram in the patient showed Ⅰ atrioventricular block; echocardiogram revealed focal hypertrophy in mitral valve with mild cardiac diastolic dysfunction; electromyogram indicated myogenic and neurogenic patterns.Muscle pathology study revealed numerous vacuoles located at the fibers.Dystrophin, merosin and C5b9 was immuno-positive around the vacuoles.Electron microscopy revealed vacuoles surrounded by sarcolemma and abnormal lysosome aggregating at the fibers.A novel nonsense mutation ( K402X ) in the LAMP2B gene has been identified in the patient but not in his mother and 50 normal controls.Conclusions Danon disease caused by K402X mutation in C-terminus of LAMP2B presented benign course of the disease characterized by prominent vacuolar skeletal myopathy, mild cardiac abnormalities and peripheral neuropathy.

Clinical and pathological features in Charcot-Marie-Tooth disease type 2A2: a family report / 中华神经科杂志

Objective To report clinical and pathological features in a Chinese family with CharcotMarie-Tooth disease type 2A2 (CMT2A2). Methods There were 5 patients (2 male and 3 female) in a family with an autosomal dominant inheritance pattern. The index case was a 36 years old woman. She developed progressive distal limb weakness at the age of 6, with pescavus at the age of 8. Other 4 family members presented with similar symptoms between the age of 3-7. Physical examination showed distal limb weakness and wasting, loss of sensory and contracture in all of them. Nerve conduction velocity revealed non-potential in several motor and sensory nerves in the proband and her son. Sural nerve biopsy was performed on the proband. The sequence of MFN2 gene was analyzed in DNA from 5 patients and 3 asymptomatic members. Results Sural nerve biopsy revealed severe loss of myelinated fibers with few regenerating clusters. Electron microscopy revealed aggregation of mitochondrian in the axons. A R94W mutation in MFN2 gene has been identified in 5 patients, but not in unaffected members. Conclusions We confirmed Chinese CMT2A2. Absent of regenerating cluster in the nerve indicated that MFN2 mutation predominantly resulted in lesions in the neurons.

Filaminopathy caused by a novel deletion-insertion mutation in filamin C gene / 中华神经科杂志

Objective To report filaminopathy with novel insertion mutation in a Chinese family.Methods Total 19 patients from successive 5 generations involved in an autosomal dominant family. The detailed clinical manifestations had been described (Chinese Journal of Neurology, 2008, 41:751-755).The filamin C gene sequencing was performed in 3 patients, 5 family members without symptoms and 50 normal persons. The amplified fragments of the exon 18 in filamin C gene were cloned into pBluesripts vectors, then sequenced and identified with capillary electrophoresis. Results 18-nucleotide deletion and 6-nucleotide insertion were identified in the exon 18 of filamin C gene. The mutation caused the disturbance of the seventh immunoglobulin-like domain in filamin C, leading to the instability of dimmers of filamin C.Another 2 patients in the family had same mutation while 5 family members without symptoms and 50 normal controls were normal. Conclusion The novel nucleotide deletion-insertion in exon 18 of filamin C gene causes filaminopathy. This disease can appear in non-Nordic race.