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.

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 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.

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.

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.

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.

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.

Objective To report clinical and pathological features in a Chinese family with desminopathy caused by a novel mutation in desmin gene. Methods There were 8 patients (7 male and 1 female) in a family manifesting desminopathy in an autosomal dominant inheritance pattern. The onset age ranged from 20--50 years old. Heart disease appeared in 7 cases, diarrhea in 1 case and limb weakness in 3 patients. Muscle biopsies were carried out in proband and his elder brother. The histological, enzymhistochemicai staining, ultrastructural examination and immunohistochemical staining with desmin antibody were performed. The sequence of desmin gene was analyzed in DNA from 4 patients, 5 asymptomatic members and 50 healthy controls. Results Muscle pathology in the proband revealed wide variation in size of fibers. Some fibers had eosinophilic changes with rimmed vacuoles. Muscle pathology in the brother revealed multiple small and round eosinophilic inclusions in the fibers. Desmin staining was positive in the inclusions and in the sarcolemma. Electron microscopy revealed deposits of abnormal granulofilamentous materials. A novel S12F mutation in desmin gene has been identified in 4 affected family individuals, but not in unaffected family members and controls. Conclusions The desminopathy caused by desmiu SI2F mutation dominantly affected male individuals. Most of victims had cardiac abnormalities. The myopatholgical features can vary in the different patients in one family.