Objective To study the clinical and neuroimaging features of subtypes of multiple system atrophy (MSA) and their correlations. Methods One hundred and forty-three MSA cases fulfilled Gilman diagnostic criteria (1999) were recruited and their clinical subtypes and stages were classified. Using the staging methods of the pontine cross sign and putaminal slit proposed by Horimoto, 108 patients showed abnormalities in MRI and were further evaluated. The relationship between the subtypes of MSA, disease duration, and MRI abnormalities has been analyzed. Results Of 143 MSA patients, the male-to-female ratio is 1.3:1 ; 93 cases are diagnosed with MSA-C, 39 with MSA-P, and 11 with MSA-P + C; 90 cases with probable diagnosis, and 53 with possible diagnosis. Of the 76 MSA-C cases with MRI abnormalities, 36 (47%) show the pontine cross sign and 10 (13%) show the putaminal slit; of the 24 MSA-P cases with MRI abnormalities, 6 (25%) show the pontine cross sign and 6 (25%) show theputaminal slit. In addition, MSA-C cases with shorter disease duration demonstrate earlier stages of the pontine cross sign. Conclusions In this study, the number of MSA-C cases is more than MSA-P, which might be related to the ethnic background. In neuroimaging, both the pontine cross sign and the putaminal slit are the marked features of MSA. To some degree, the subtypes of MSA are related with the features of imaging, that is, MSA-C patients present the pontine cross sign more often than MSA-P, and the putaminal slit is a comparatively common feature among MSA-P cases.

Objective To study the correlation between clinical rating scale and the duration of multiple system atrophy.Methods One hundred and twenty-two MSA cases fulfilling Gilman diagnostic criteria were recruited.Unified Multiple System Atrophy Rating Scale(UMSARS)was applied to assess the degree of the patients' disability.For analyzing the correlation between the UMSARS scores and the duration of the disease,the Spearman's rank correlation coefficients were calculated.Results Among 122 MSA cases,male:female ratio was 1.7:1;disease duration lasted(2.8±1.6)years:possible MSA accounted for 50 cases(41%),probable MSA 72 cases(59%);MSA-P 35 cases(29%);MSA-C 73 cases(60%).MSA-P+C 5 cases(4%),MSA-A 9 cases(7%).The scores of UMSARS,UMSARS-Ⅰ and UMSARS-Ⅱ were found positively correlating with the disease duration.The Spearman's rank correlation coefficients were 0.368,0.266 and 0.392 respectively,all P<0.01;the adjusted Spearman's rank correlation coefficients were 0.360,0.257 and 0.385 respectively.all P<0.01.Conclusions MSA has complex clinical manifestations.which should include MSA-P+C subtype.UMSARS is a reliable scale to mirror the progression of MSA.which is useful to study the clinical features and disease duration of MSA.

Objective To analyze plasma vitamin E and CoQ10 levels in patients with autosomal recessive cerebellar ataxia for finding the evidence of the related pathogenesis research and therapeutic strategies.Methods The plasma vitamin E and CoQ10 levels were detected by high performance liquid chromatography (HPLC) with diode array detector in 123 probands of autosomal recessive cerebellar ataxia pedigrees.Quantitation was performed using vitamin E and CoQ10 external standard and two 5-point calibration curve;clinical manifestations were analyzed simuhaneously.Results Vitamin E and CoQ10 levels of healthy subjects in the plasma were (8.77 ± 2.28) μg/ml and (1.31 ± 0.38) μg/ml,respectively;the plasma vitamin E and CoQ10 levels of patients were (5.61 ± 2.04) μg/ml and (0.79 ± 0.26) μg/ml,respectively,which were significantly lower than those in healthy controls (t =11.87,13.15;all P＜ 0.01).Clinical manifestations were characterized by cerebellar symptoms,and gait instability was usually the first recognized abnormality.Most of early onset occurred before the age of 25 years (111/123);dysarthria and abnormal eye movement were observed,with cerebellar atrophy on MRI;concomitant symptoms were also present.Conclusions HPLC analysis shows that the plasma vitamin E and CoQ10 levels of patients with autosomal recessive cerebellar ataxia are generally lower than those in the healthy controls.Several patients with significant reductions in these two levels have genetic defects.The combination of clinical phenotypes,biochemical indexes and genetic analyses will be helpful for the establishment of diagnosis and specific treatment.

Objective To investigate the inheritance principle of the expanded GAG repeat allele and the clinical features of spinocerebellar ataxias 3 (SCA3) in a consanguinity family with first cousin marriage.Methods The CAG repeats of SCA3 gene were amplified by means of polymerase chain reaction.Fragment analysis with laser-induced fluorescence in capillary electrophoresis were performed for the positive samples detected by agarose gel electrophoresis.Furthermore,the clinical features were analyzed carefully.Results Fragment analysis revealed that the proband carried 2 alleles with 56 and 72 CAG repeats separately.The proband' s father carried 28 and 66,and the expanded CAG repeat allele inherited from his grandfather.The proband' s mother carried 33 and 56,and the expanded CAG repeat allele inherited from his grandmother.The proband' s son carried 27 and 85 and presented with dystonia besides ataxia.Conclusions The proband' s parents have the common ancestors.Their alleles with expanded CAG repeats probably come from the same allele of their ancestor.The GAG repeat is more unstable in the paternal inheritance than in the maternal inheritance.The 71-year-old asymptomatic family member carry the allele with 56 CAG repeats,which indicates the 56 CAG repeats may be not associated with the disease.The patients within this family have variable clinical features,especially the juvenile-onset case presents with apparent dystonia.

The plasma ammo acid levels in 21 centenarians(age 100-106), 21 elders (age 65-78) and 37 young human subjects (age 18-21) were determined. 17 of 24 amino acids studied showed lower values in centenarian and elder groups than those in young group (p

Objective Mitochondrial transfer RNA for leucine 1(MTTL1)is one of the most important causative genes of oxidative phosphorylation disorders.To understand the clinical,pathological and molecular genetics features of the disordel's caused by MTTL1 mutation.18 patients with a causative mutation in MTTL1 were analyzed.Methods The clinical features,the findings of tlleir biochemistry tests.the neuroimagings,the pathology of biopsied muscles and hereditary characteristics were retrospectively summarized.Results The mutations mt3243A>G and mt3271A>T within MTTL1 gene led to variant syndrome,encephalomyopathies with lactic acidosis and stroke like episodes,diabetes mellitus,progressive external ophthalmoplegia,leish syndrome and complex mitochondrial syndrome were reported.Usually,most patients were sporadic but maternal transmission was the common inherited model.Conclusion The disorders caused by the MTTL1 mutation are hishly phenotypic vailable.There is no association between phenotype and heteroplasmy in muscle.

Objective To investigate the characteristics of PMP22 duplication mutation and the clinical variability of Charcot-Marie-Tooth disease type 1A (CMT1A) patients. Methods PMP22 duplication mutation analysis were performed in 45 cases diagnosed probably CMT by combination of improved allele-specific PCR-restriction enzyme digestion and short tandem repeat (STR) analysis based on laser-induced fluorescence detection in capillary electrophoresis. The clinical features of the positive cases were precisely analyzed. Results With the combined use of two methods, PMP22 duplication was detected in 21 cases, i.e. 10 CMT1 cases with typical presentations including weakness and atrophy in the distal limbs, and 11 atypical cases with special phenotypes including 1 case with mild dizziness, 1 case with hearing loss, 2 cases with recurrent limbs weakness, 2 cases with postural tremor in the upper limbs, 4 cases with cerebellar ataxia and 1 case with epilepsy. Conclusions The improved allele-specific PCR-restriction enzyme digestion provides the accurate, reliable and feasible method to detect PMP22 duplication, which is the most common cause of CMT. Comprehensive analysis of clinical, electrophysiological and pathological features of the CMT1A patients with positive PMP22 duplication indicate the high clinical variability of this disease.

Objective To investigate the clinical features and genetic mutations of spinocerebellar ataxia type 17 (SCA17).Methods The pathological CAG triplet repeat expansions of the SCA3,SCA1,SCA2,SCA6,SCA7,SCA8,SCA12,SCA17 and dentatorubral pallidoluysian atrophy genes were analyzed in 708 probands of autosomal dominant familial SCA and 1 19 sporadic SCA cases.The CAG repeats of TATA-binding protein (TBP) gene were amplified by means of polymerase chain reaction and agarose gel electrophoresis.For the samples with two alleles,fragment analysis based on CEQ8000 sequencer was applied to analyze the CAG repeat numbers.Furthermore,the correlation between clinical features and CAG repeat in the TBP gene was studied carefully.Results The expanded CAG repeats in the TBP gene was detected in 5 cases with 37/50,36/45,38/52,38/53,36/54 separately.And the main clinical manifestations were ataxia and memory impairment.Conclusion These findings indicate that SCA17 might be a rare subtype of SCA in the Chinese population and the clinical features of SCA17 cover a wider spectrum than previously reviewed.

Objective To investigate methods for prenatal diagnosis of spinocerebellar ataxia type 3 (SCA3).Methods Cordocentesis were performed in the pregnant SCA3 female proband of pedigree during the 20th gestational week.Polymerase chain reaction (PCR) and short tandem repeat (STR) analysis based on CEQS000 sequencer were applied to analyze the CAG repeat of SCA3 gene.Results The proband had 31/75 CAG repeat alleles of SCA3 gene; her spouse had 14/27 CAG repeat alleles; the fetuse had 14/31 CAG repeat alleles (14 repeat from the father,and 31 repeat from the mother),which is in conformity with Medelian inheritance.The fetuse inherited the normal CAG repeat allele from the mother.The above results of the fetuse were verified after its birth.Conclusion Detecting CAG repeat dynamic mutation of SCA3 gene based on umbilical cord blood and STR analysis could be a rapid and reliable method for prenatal diagnosis of SCA3.

Objective To observe the level of imprinting gene p57kip2 and p27kip1 expression in different hydatidiform moles.To investigate the value of combined detection of p57kip2 and p27kip1 in diagnosis and differential diagnosis of hydatidiform moles.Methods We examined the immunohistochemical staining of p57kip2 and p27kip1 in 30 cases of complete hydatidiform moles and 86 cases of partial hydatidiform moles and 30 cases normal placenta,and also analyze the differences and correlation between the two genes of p57kip2 and p27kip1 in two different patterns of hydatidiform moles.Results The rate of expression of p57kip2 and p27kip1 in complete hydatidiform moles was obviously lower than that in partial hydatidiform moles and nor-mal placenta.There were significant differences in the expression of p57kip2 and p27kip1 among complete hy-datidiform moles,partial hydatidiform moles and normal placenta(P<0.05).p57kip2 had positive correlation with p27kip1 in complete hydatidiform moles(r=0.750,P<0.01),meanwhile there was negative correlation between p57kip2 and p27kip1 in partial hydatidiform moles(r= -1.000,P<0.01).Conclusion The differen-tial expression of p57kip2 and p27kip1 in complete hydatidiform moles and partial hydatidiform moles can be of certain value in the differential diagnosis of hydatidiform moles.Meanwhile,the combined methed is useful to the identification and classification of hydatidiform moles.