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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.
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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.
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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.
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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.