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 report the clinical, myopathological and genetic features in myofibrillar myopathy (MFM) with numerous cytoplasmatic-spheroid bodies. Methods Ten patients in 5 successive generations began to present progressive proximal limbs weakness at 35 to 40 years old. Additionally, 4 cases manifested diarrhea and 6 cases accompanied with cardiorespiratory symptoms. An open biopsy was performed on the proband. In addition to histological, enzymhistochemical staining and ultrastructural examination, immunohistochemical staining with antibody against tau, desmin, ubiquitin, dysferlin, dystrophin-C', dystrophin-N' and dystrophin-R were done. All the exons of the MYOT, CRYAB, DESMIN, LDB3, LMNA, SEPNI gene and the FLNC exon 48 were analysed. Results Cytoplasmatic bodies and spheroid bodies were found in the fibers. The deposited material were positive for tau, desmin, ubiquitin, dysferlin and dystrophin-R, dystrophin-C'. Electron microscope showed granular dense Z-disc material in the inclusions which were surrounded by thin filament. There was no mutation in the above exons of the 7 candidate genes. Conclusions Myofibrillar myopathy involves multiple system impairment. Cytoplasmatic and spheroid bodies contain microtubule and membrane associated protein. The disease might be induced by some unknown genetic abnormities.

ObjectivesTo report pathological and genetic features of 6 Chinese families with Xlinked Charcot-Marie-Tooth disease type 1 ( CMTX1 ).Methods The index cases from 6 families with CMTX1 are males with onset of disease between 11 and 24 years old.All of them had distal leg muscle weakness,accompanied with areflexia and sensory loss in the feet.Additionally,the index 1 presented with recurrent encephalopathy and the index case 5 with cerebellar ataxia.Peripheral neuropathy was found in 12 family members,while other 7 members showed talipescavus and hyporeflexia.Sural nerve biopsies were performed in all index cases.Connexin 32(Cx32) gene was analyzed in the index cases,8 affected and 10unaffected family members as well as 50 healthy women control subjects.ResultsMild to moderate loss of myelinated fiber with axonal degeneration and regeneration clusters were found in all index cases. Thin myelin fibers were found in 5,small onion bulbs in 3 and inflammatory infiltrates in 2.Five novel mutations (I20T,I127F,D178G,A197V,403_404insT) and one L10L synonymous mutation were detected in the 6index cases and their affected family members.The same mutations,in heterozygous state,were detected in 4 female family members without clinical symptoms,but not found in 6 male unaffected family members.The same mutations were not found in healthy control subjects.ConclusionsThe CMTX1 patients in our study present predominantly axonal lesions.Frequent novel Cx32 gene mutations indicated that private mutations may be common in Chinese CMTX1 patients.

Objective To describe the clinical, radiological and genetic features in a family with X-linked Charot-Marie-Tooth disease type 1 (CMT1X) with transient white matter lesions.Methods The proband is a 14-year-old boy who presented transient and recurrent dysarthria, mild numbness and weakness of the limbs for 2 years and 5 months.Later he developed leg weakness.His mother only presented pes cavus.MRI, electrophysiology and nerve biopsy were performed in the proband.Gap junction protein beta 1 (GJB1) gene was analyzed by PCR-sequencing on the proband, his parents and 50 non-illness control women.Results Electremyography showed marked reduced amplitude of the distal compound muscle action potentials and mild decrease of conduction velocities.MRI showed bilateral white matter lesions in centrum semiovale and corpus callnsum, which improved significantly after 6 months.Pathological examination revealed chronic axonal neuropathy and widened Schmidt-Lanterman incisures of myelinated fibers.I20T mutation in GJB1 gene was detected in the proband and his mother, but not in non-illness control women and his father.Conclusions Novel 120T mutation of GJBI maybe could result in CMT1X with predominant recurrent leucocncephalopathy.The white matter changes in MRI are reversibility.

Objective To describe the changes of cell development associated contracture and structure proteins in vascular smooth muscle cells (VSMCs) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods The clinical manifestation of probands in 6 families showed the recurrent cerebral ischemic event. A part of patients showed dementia. The genetic analysis in all probands showed Notch3 gene mutation. All probands received the sural nerve biopsy. The primary antibodies against α-smooth muscle actin, smooth muscle myosin heavy chain, desmin and vimenfin were used in immunohistochemistry staining on all of them. Results VSMCs showed hypertrophy or atrophy in the arterioles with different caliber. The granular osmiophilic material (GOM) could be found within the basal lamina of arteriole VSMCs in all of the probands. The expressions of α-smooth muscle actin and smooth muscle myosin heavy chain were partly lost, negative or unevenly distributed in the VSMCs in the arteriole. The expression of desmin showed also unregular distribution or partial loss. The expression of vimentin was partly enhanced. Conclusions The VSMCs show the physiological features of synthetic configuration, indicating the hypoplasia of VSMCs in the arterioles of CADASIL. The VSMCs of the larger arteriole were more severely involved.

Objective To report the clinical, pathological and genetic features in a Chinese family with distal hereditary motor ueuropathy type Ⅴ (dHMN-Ⅴ). Methods Four men and 5 women in 4 generations were involved. The onset of disease was from 13 to 40 years old. Six of them showed predominantly weakness of low extremities. Two women had only weakness and atrophy of hand muscle and 1 woman presented additionally pyramidal signs. The proband, a 20 year-old girl, presented asymmetrical atrophy and weakness of both hands since 13 years old. She had weakness of low extremities after 15 years old. Neurogenic changes were observed in the electromyography. Amplitude of compound muscle action potentials were markedly reduced, while the motor nerve conduction velocity were mildly decreased. Sensory nerve conduction velocity and amplitude of action potential were within the normal range. Sural nerve biopsy was performed in the proband. Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) gene were sequenced in the proband and other 4 patients. Results Nerve biopsy showed mild loss of myelinated fibers with a few regeneration cluster of myelinated fibers. DNA analysis revealed a heterozygons 263A→G mutation in exon 3 of BSCL2 gene. Conclusions dHMN-V has been genetically and clinically confirmed in this family. The phynotype is obviously heterogeneous in onset time and clinical symptoms within the same family. The patients present mild pyramidal tract signs and axonal lesions in the sensory nerve.

Objective To report clinical,myopathological and genetic features in a family with oculopharyngeal muscular dystrophy(OPMD).Methods The proband,a 60 year-old man,presented proximal weakness of both lower limbs since 50 years old.He developed dysphagia and dysarthria after 53 years old and mild exophthalmos with ptosis after 57 years old.The serum creatine kinase was mildly elevated.Electromyography showed neurogenic involvement and the nerve conduction velocity decreased 20%-143%.Other 5 members in 3 generations developed also dysathria after 45 years old.followed by ptosis 4-20 years afterwards.Three of them showed mild limb weakness.Muscle was biopsied in the proband and specimen was examined with histological,enzymhistochemical,immunohistochemical stainings (first antibody were anti.desmin and ubiquitin antibedies) and ultrastructural examination.PABPN1 gene was sequenced in the proband and 18 family members.Results Rimmed vacuoles with ubiquitin positive material appeared in the muscle fibers.Additionally.there were a few angular atrophic fibers in small groups,COX negative fibers and desmin positive regenerative fibers.Intranuclear palisading filamentous inclusions were observed electromicroscopically in 3% of the nuclears.(GCG)6in PABPN1 was expanded to (GCG)9 in the proband and 11 members.Conclusions The onset symptoms is pharyngeal weakness in OPMD due to heterozygous expanding of PABPNl(GCG)9,accompanied with demyelinating neuropathy.Intranuclear inclusions are also identified in Chinese patient.

Objective To assess retinal arteriole stenosis in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and to evaluate the relationship between retinal arteriole stenosis with cranial MRI changes and clinical features. Methods Sixteen CADASIL patients (mean age was (43.4±8.1)years, mean duration was(4.7±3.4)years)and sixteen age matched healthy individuals were enrolled. Mini-Mental State Examination (MMSE) and modified Rankin scale scoring were performed in 16 patients. Cranial MRl with Coulthard scores was assessed on CADASIL patients as well. Retinal examinations for arteriole stenosis were done for each subject. Bivariate correlations (Kendall's tau-b) were used to assess the relationship among the grade of retinal stenosis, MMSE, modified Rankin seale, cranial MRI with Coulthard scores and age. Results Retinal arteriole stenosis presented in 15 cases. in whom 4 cases showed mild arterio-venous nicking. while it only presented in 2 controls. Grade 0.Ⅰ, and Ⅲ of retinal arteriole stenosis are noted in 1/16,4/16,7/16 and 4/16cases respectively. Coulthard scores of cerebral MRl were 6.0.19.0.25.1 and 29.8 respectively from Grade 0 toⅢ of retinal arteriole stenosis. The correlation coefficient of retinal arteriole stenosis and cranial MRI scores was 0.743(P＜0.001＝,MMSE-0.429(P＜0.05＝,modified Rankin scale 0.437(P＞0.05).and age 0.299(P＞0.05).Conclusion Retinal arteriole stenosis is significantly correlated with lesion in cranial MRI and dementia.

Objectives To report clinical,electrophysiological and pathological features of myopathy with tubular aggregates.Methods The onset of the disease was between 5-50 years old in the 6 sporadic male cases.Skeletal muscle biopsy was performed for all cases.Specimens were examined histochemically,enzymhistochemically and electromicroscopically.Results Case 1 and 2 presented with limb girdle myasthenic syndrome.The case 1 developed exercise-induced cramps in the late stage.Case 3 complained about persistent weakness and Dopa-responsive dystonia.Case 4 and 5 were characterized by periodic paralysis.Case 6 showed exercise-induced cramps.Serum potassium was normal in all patients. Slight elevation of serum creatine kinase appeared in 3 cases.Electromyography showed neurogenic pattern in case 1 and 6,myogenic changes in case 4 and 5,and no abnormality in other 2 cases.Marked decrement of active potential amplitude was noted with low frequency repetitive nerve stimuli in case 1 and 2.Four percent to forty percent of muscle fibers showed focal material accumulation in the fibers,which involved mainly type 2 fibers in all cases.The material was stained bright red material with modified gomori trichrome,intensive staining with nicotinamide adenine dinucleotide-tetrazolium reductase,lack activity of succinate dehydrogenase and ATPase.Electron microscopy confirmed bundles of parallel micro-tubular structure in the muscle fiber.Conclusions Myopathy with tubular aggregates has various clinical subtypes and electromyographic pattern.Dystonia or other systemic symptoms could be noted in this disease.The limb girdle myasthenic syndrome can also be accompanied with exercise-induced cramps.

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.