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.

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.

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.

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.

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.

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.

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.

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.

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.

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.